Omid Farokhzad

KWVJHCQQUFDPLU-YEUCEMRASA-N 2, 3-bis [[(z)-octadec-9-enoyl] oxy] propyl-trimethylazanium Chemical compound CCCCCCCC\C= C/CCCCCCCC (= O) OCC (C [N+](C)(C) C) OC (= O) CCCCCCC\C= C/CCCCCCCC KWVJHCQQUFDPLU-YEUCEMRASA-N 0.000 description 10

Advancements in deep plasma proteomics are enabling high-resolution measurement of plasma proteoforms, which may reveal a rich source of novel biomarkers previously concealed by aggregated protein methods. Here, we analyze 188 plasma proteomes from non-small cell lung cancer subjects (NSCLC) and controls to identify NSCLC-associated protein isoforms by examining differentially abundant peptides as a proxy for isoform-specific exon usage. We find four proteins comprised of peptides with opposite patterns of abundance between cancer and control subjects. One of these proteins, BMP1, has known isoforms that can explain this differential pattern, for which the abundance of the NSCLC-associated isoform increases with stage of NSCLC progression. The presence of cancer and control-associated isoforms suggests differential regulation of BMP1 isoforms. The identified BMP1 isoforms have known functional differences, which may reveal insights into mechanisms impacting NSCLC disease progression.

2023-02-24 Assigned to SEER, INC. reassignment SEER, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: KIM, SANGTAE, HARRIS, DAMIAN, BLUME, JOHN E., Hornburg, Daniel, SIDDIQUI, Asim S., DONOVAN, Margaret, FAROKHZAD, OMID C., FIGA, MICHAEL, GOLDBERG, MARTIN, PLATT, Theodore, ZHAO, XIAOYAN, MA, PHILIP

The present disclosure provides a system comprising a communication interface and computer for assigning a label to the biomolecule fingerprint, wherein the label corresponds to a biological state. The present disclosure also provides a sensor arrays for detecting biomolecules and methods of use. In some embodiments, the sensor arrays are capable of determining a disease state in a subject.

With the integration of nanotechnology into the medical field at large, great strides have been made in the development of nanomedicines for tackling different diseases, including cancers. To date, various cancer nanomedicines have demonstrated success in preclinical studies, improving therapeutic outcomes, prolonging survival, and/or decreasing side effects. However, the translation from bench to bedside remains challenging. While a number of nanomedicines have entered clinical trials, only a few have been approved for clinical applications. In this review, we highlight the most recent progress in cancer nanomedicine, discuss current clinical advances and challenges for the translation of cancer nanomedicines, and provide our viewpoints on accelerating clinical translation. We expect this review to benefit the future development of cancer nanotherapeutics specifically from the clinical perspective.

2018-08-07 Assigned to THE BRIGHAM AND WOMEN'S HOSPITAL, INC. reassignment THE BRIGHAM AND WOMEN'S HOSPITAL, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: FAROKHZAD, OMID C., ZHANG, XUE-QING

Disclosed herein are systems and methods of use thereof for coupling affinity reagents (eg, in solution affinity reagents such as proteins, peptides, and nucleic acids and libraries of affinity reagents) with particles having coronas for rapid detection of proteins in a sample.

Corrigendum to "Redox-responsive polyprodrug nanoparticles for targeted siRNA delivery and synergistic liver cancer therapy" [Biomater. 234 (2020) 119760] Corrigendum to "Redox-responsive polyprodrug nanoparticles for targeted siRNA delivery and synergistic liver cancer therapy" [Biomater. 234 (2020) 119760] Biomaterials. 2023 Feb:293:121951. doi: 10.1016/j.biomaterials.2022.121951. Epub 2022 Dec 14. Authors Senlin Li 1 , Phei Er Saw 2 , Chunhao Lin 2 , Yan Nie 2 , Wei Tao 3 , Omid C Farokhzad 4 , Lei Zhang 5 , Xiaoding Xu 6 Affiliations 1 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, PR China; RNA Biomedical Institute, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, PR China; Department of Hepatobiliary Surgery, …

Disclosed herein are biomarkers associated with a disease state such as lung cancer, and methods of discovering or using biomarkers. Also disclosed herein are classifiers built on biomarkers and methods of detecting the disease state in samples from subjects. The method may include obtaining a data set that includes protein information from a biofluid sample, and may involve using a classifier to identify the sample as indicative of a healthy state, a disease state, or a comorbidity.

Self-assembled gel compositions including a gelator, eg, an enzyme-cleavable gelator, eg, having a molecular weight of 2500 or less, are described. The self-assembled gel compositions can encapsulate one or more agents. Methods of making the self-assembled gel compositions, and methods of drug delivery using the self-assembled gel composi-tions are also described.

2020-10-27 Assigned to THE BRIGHAM AND WOMEN'S HOSPITAL, INC. reassignment THE BRIGHAM AND WOMEN'S HOSPITAL, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: ALEXIS, FRANK, FAROKHZAD, OMID C.

Disclosed herein are particles and methods of using said particles in assays for detection of biomolecules in a sample. Various methods of the present disclosure utilize particles for biomolecule adsorption. In some aspects, the present disclosure provides methods which utilize multiple particle concentrations to differentially fractionate biological samples. In further aspects, the present disclosure provides methods which utilize low particle concentrations to enhance adsorbed biomolecule diversity.

Disclosed herein are compositions and methods for assaying for low volumes of proteins and/or nucleic acids, optionally in parallel.

The effectivity of cancer immunotherapies is hindered by immunosuppressive tumour microenvironments that are poorly infiltrated by effector T cells and natural killer cells. In infection and autoimmune disease, the recruitment and activation of effector immune cells is coordinated by pro-inflammatory T helper 17 (TH17) cells. Here we show that pathogen-mimicking hollow nanoparticles displaying mannan (a polysaccharide that activates TH17 cells in microbial cell walls) limit the fraction of regulatory T cells and induce TH17-cell-mediated anti-tumour responses. The nanoparticles activate the pattern-recognition receptor Dectin-2 and Toll-like receptor 4 in dendritic cells, and promote the differentiation of CD4+ T cells into the TH17 phenotype. In mice, intra-tumoural administration of the nanoparticles decreased the fraction of regulatory T cells in the tumour while markedly increasing the fractions of TH17 cells (and …

2020-08-25 Assigned to THE BRIGHAM AND WOMEN'S HOSPITAL, INC. reassignment THE BRIGHAM AND WOMEN'S HOSPITAL, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: FAROKHZAD, OMID, WU, JUN, ZHAO, LILI

Background:The wide dynamic range of circulating proteins coupled with the diversity of proteoforms present in plasma has historically impeded comprehensive and quantitative characterization of the plasma proteome at scale. Automated nanoparticle (NP) protein corona-based proteomics workflows can efficiently compress the dynamic range of protein abundances into a mass spectrometry (MS)-accessible detection range. This enhances the depth and scalability of quantitative MS-based methods, which can elucidate the molecular mechanisms of biological processes, discover new protein biomarkers, and improve comprehensiveness of MS-based diagnostics.Methods:Investigating multi-species spike-in experiments and a cohort, we investigated fold-change accuracy, linearity, precision, and statistical power for the using the Proteograph™ Product Suite, a deep plasma proteomics workflow, in conjunction with …

We have developed a scalable system that leverages protein-nano interactions to overcome current limitations of deep plasma proteomics in large cohorts. Introducing proprietary engineered nanoparticles (NPs) into a biofluid such as blood plasma leads to the formation of a selective and reproducible protein corona at the particle-protein interface, driven by the relationship between protein-NP affinity and protein abundance. Here we demonstrate the importance of tuning the protein to NP-surface ratio (P/NP), which determines the competition between proteins for binding. We demonstrate how optimized P/NP ratio affects protein corona composition, ultimately enhancing performance of a fully automated NP-based deep proteomic workflow (Proteograph). By limiting the available binding surface of NPs and increasing the binding competition, we identify 1.2 – 1.7x more proteins with only 1% false discovery rate on the surface of each NP, and up to 3x compared to a standard neat plasma proteomics workflow. Moreover, increased competition means proteins are more consistently identified and quantified across replicates, yielding precise quantification and improved coverage of the plasma proteome when using multiple physicochemically distinct NPs. In summary, by optimizing NPs and assay conditions, we capture a larger and more diverse set of proteins, enabling deep proteomic studies at scale.

2022-04-08 Assigned to THE BRIGHAM AND WOMEN'S HOSPITAL, INC. reassignment THE BRIGHAM AND WOMEN'S HOSPITAL, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: FAROKHZAD, OMID C., SHI, JINJUN, XU, XIAODING

In article number 2206008, Omid C. Farokhzad, Daniel Hornburg, and co-workers show how the Vroman effect can be leveraged to capture the complexity of human proteomes using engineered nanoparticles. Protein corona formation dynamics demonstrate how nanoparticle functionalization and nano–bio binding competition enable deep and quantitative interrogation of biosamples. This facilitates increased capture of low-abundance proteins, including cytokines and chemokines, enabling new strategies for biomarker discovery and personalized nanomedicine.

Comprehensive assessment of the human proteome remains challenging due to multiple forms of a protein, or proteoforms, arising from alternative splicing, allelic variation, and protein modifications. As proteoforms can serve distinct functions and act as functional links between genotype and phenotype, proteoform-level knowledge is critical in understanding the molecular mechanisms underlying health and disease. However, identification of proteoforms requires unbiased protein coverage at amino acid resolution. Scalable, deep, and unbiased proteomics studies have been impractical due to cumbersome and lengthy workflows required for complex samples, like blood plasma. Here, we demonstrate the power of the Proteograph™ Product Suite in enabling unbiased, deep, and rapid proteomics at scale in a proof-of-concept proteoform analysis to dissect differences between protein isoforms in plasma samples from 80 healthy controls and 61 patients with early-stage non-small-cell lung cancer (NSCLC). Processing the 141 plasma samples with Proteograph yielded 22,993 peptides corresponding to 2,569 protein groups at a confidence of 1% false discovery rate. We extracted four proteins with peptides with significant abundance differences (p < 0.05; Benjamini-Hochberg corrected) in healthy control and cancer plasma samples. For one, the abundance variation can be explained by underlying annotated protein isoforms. For a second, we find evidence for differentially transcribed isoforms in the broader sequence data, but not in the known annotated protein isoforms. The others may be explained by novel isoforms or post-translational …

Introduction: Comprehensive assessment of the proteome remains elusive because of proteoforms arising from alternative splicing, allelic variation, and protein modifications. Characterization of the variable protein forms, or proteoforms will expand our understanding of the molecular mechanisms underlying diseases, however requires unbiased protein coverage at sufficient scale. Scalable, deep and unbiased proteomics studies have been impractical due to cumbersome and lengthy workflows required for complex samples, like blood plasma. Here, we demonstrate the power of Proteograph in a proof-of-concept proteogenomic analysis of 80 healthy controls and 61 early-stage non-small-cell lung cancer (NSCLC) samples to dissect differences between protein isoforms arising from alternative gene splicing, as well as the identification of novel peptides arising from allelic variation. Materials, Methods and Results …

Nanoparticles exposed to biological fluids such as blood, quickly interact with their surrounding milieu resulting in a biological coating that results in large part as a function of the physicochemical properties of the nanomaterial. The large nanoparticle surface area-to-volume ratio further augments binding of biological molecules and the resulting biomolecular or protein corona, once thought of as problematic biofouling, is now viewed as a rich source of biological information that can guide the development of nanomedicines. This review gives an overview of the utility of the protein corona in proteomic profiling and discusses how a better understanding of nano-bio interactions can accelerate the clinical translation of nanomedicines and facilitate the identification of disease-specific biomarkers. With the FDA requirement of the protein corona analysis of nanoparticles in place, it is envisaged that analyzing the protein …

Described herein are methods and systems for identifying protein-protein interactions using particle panels and protein corona formation. Also disclosed herein are systems and methods for enrichment analysis between protein annotations and particle biophysicochemical properties.

Over the past two decades, the rapid development of versatile inorganic/organic fluorophores or biomaterials in the second near-infrared (NIR-II) window (1000− 1700 nm) contributed significantly to the rapid progress of theranostic nanomedicine, which is integrated with diagnosis and therapy functions to improve treatment outcomes (via imaging-guided combination therapy, drug-release monitoring, therapeutic response monitoring, etc.). The NIR-IIA/IIB window could be further split into two subwindows, ie, NIR-IIa (1300− 1400 nm) and NIR-IIb (1500− 1700 nm), by a water overtone absorption peak (at∼ 1450 nm). Compared with fluorescence imaging in the first near-infrared (NIR-I) window (750− 900 nm), imaging in the NIR-IIA/IIB window with a longer wavelength can achieve lower photon scattering and even a near-zero diminishment of fluorescence in the NIR-IIb window, yielding high-resolution deep-tissue …

Disclosed herein are methods and compositions for processing biofluid samples. Some such methods may include obtaining a biofluid sample from a subject having a disease state such as lung cancer. The biofluid sample may be contacted with a nanoparticles to adsorb proteins. The proteins may then be ionized or contacted with a detection reagent. Also disclosed herein are compositions comprising proteins coupled to a nanoparticle upon contact of the nanoparticle with a biofluid sample from a subject having a disease.

Deep interrogation of plasma proteins on a large scale is a challenge due to the number and concentration of proteins, which span a dynamic range of over 10 orders of magnitude. Current plasma proteomics workflows employ labor-intensive protocols combining abundant protein depletion and sample fractionation. We previously demonstrated the superiority of multinanoparticle (multi-NP) coronas for interrogating the plasma proteome in terms of proteome depth compared to simple workflows. Here we show the superior depth and precision of a multi-NP workflow compared to conventional deep workflows evaluating multiple gradients and search engines as well as data-dependent and data-independent acquisition. We link the physicochemical properties and surface functionalization of NPs to their differential protein selectivity, a key feature in NP panel profiling performance. We find that individual proteins and …

6,129,761 A 6,468,798 B1 6,491,666 B1 6,527,762 B1 6,858,229 B1 6,976,982 B2 7,226,442 B2 7,604,628 B2 8,008,449 B2 8,476,246 B2 8,591,900 B2 8,790,655 B2 8,795,678 B2 9,073,994 B2 9,388,418 B2 9,549,901 B2 10,583,091 B2 11,090,367 B2 11,123,304 B2 2003/0165499 A1 2004/0120948 A1 2006/0002852 A1 2007/0148163 A1 2009/0028910 A1 2011/0271358 Al 2013/0011333 Al 2013/0011405 A1 2013/0315831 A1 2013/0344158 Al 2015/0247145 Al 2016/0206750 A1* 2016/0243048 A1

A method for treating a cancer involving one or more translocations generating an oncogenic fusion transcription factor that requires p300/CBP for activity in an animal, comprising administering a compound of formula (I):

G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, eg cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolitesG01N33/57488—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, eg cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds identifable in body fluids

As the population affected by Alzheimer's disease (AD) grows, so does the need for a noninvasive and accurate diagnostic tool. Current research reveals that AD pathogenesis begins as early as decades before clinical symptoms. The unique properties of nanoparticles (NPs) may be exploited to develop noninvasive diagnostics for early detection of AD. After exposure of NPs to biological fluids, the NP surface is altered by an unbiased but selective and reproducible adsorption of biomolecules commonly referred to as the biomolecular corona or protein corona (PC). The discovery that the plasma proteome may be differentially altered during health and disease leads to the concept of disease‐specific PCs. Herein, the disease‐specific PCs formed around NPs in a multi‐NPs platform are employed to successfully identify subtle changes in plasma protein patterns and detect AD (>92% specificity and ≈100 …

Increasing clinical evidence has demonstrated that the deletion or mutation of tumor suppressor genes such as the gene-encoding phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in cancer cells may correlate with an immunosuppressive tumor microenvironment (TME) and poor response or resistance to immune checkpoint blockade (ICB) therapy. It is largely unknown whether the restoration of functional PTEN may modulate the TME and improve the tumor’s sensitivity to ICB therapy. Here, we demonstrate that mRNA delivery by polymeric nanoparticles can effectively induce expression of PTEN in Pten-mutated melanoma cells and Pten-null prostate cancer cells, which in turn induces autophagy and triggers cell death–associated immune activation via release of damage-associated molecular patterns. In vivo results illustrated that PTEN mRNA nanoparticles can reverse the …

In article 20210011, Claudia Corbo, Wei Tao, and co-workers present an overview of common causes of bone defects, the unmet clinical needs, and the utility of biomaterials and nanotechnology to facilitate bone regeneration. The authors propose several key approaches to improve bone repair strategies that guide the future research direction of bone repair to improve treatment.

Synthetic mRNA represents an exciting cancer vaccine technology for the implementation of effective cancer immunotherapy. However, inefficient in vivo mRNA delivery along with a requirement for immune co-stimulation present major hurdles to achieving anti-tumor therapeutic efficacy. Here, we demonstrate a proof-of-concept adjuvant-pulsed mRNA vaccine nanoparticle (NP) that is composed of an ovalbumin-coded mRNA and a palmitic acid-modified TLR7/8 agonist R848 (C16-R848), coated with a lipid-polyethylene glycol (lipid-PEG) shell. This mRNA vaccine NP formulation retained the adjuvant activity of encapsulated C16-R848 and markedly improved the transfection efficacy of the mRNA (>95%) and subsequent MHC class I presentation of OVA mRNA derived antigen in antigen-presenting cells. The C16-R848 adjuvant-pulsed mRNA vaccine NP approach induced an effective adaptive immune response …

Provided herein relates to methods and systems of a com plex biomolecule sampling using machine learning algo rithms. The methods and systems provided herein can aid in selection of previously unknown biomarkers and provide a report comprising a score or probability relating to a speci fied biological state. The methods and systems provided herein can aid in the rational design of particles to capture biomarkers.

2020-07-30 Assigned to THE BRIGHAM AND WOMEN'S HOSPITAL, INC. reassignment THE BRIGHAM AND WOMEN'S HOSPITAL, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: XU, XIAODING, FAROKHZAD, OMID, SHI, JINJUN

2D stanene-based nanosheets (SnNSs) serving as a new type of sonosensitizer for ultrasound-mediated sonodynamic therapy are reported by Omid C. Farokhzad, Wei Tao, Tian Xie et al. in their Research Article on page 7155. SnNSs could also serve as robust photothermal agents and carriers for photothermal therapy and β-elemene delivery. This study not only presents a strategy for the large-scale synthesis of SnNSs but also establishes general platforms for tri-modal combination cancer therapy.

The present disclosure provides sensor arrays for detecting biomolecules and methods of use. In some embodiments, the sensor arrays are capable of determining a disease state in a subject.

Aims Recent evidence suggests that ‘vulnerable plaques’, which have received intense attention as underlying mechanism of acute coronary syndromes over the decades, actually rarely rupture and cause clinical events. Superficial plaque erosion has emerged as a growing cause of residual thrombotic complications of atherosclerosis in an era of increased preventive measures including lipid lowering, antihypertensive therapy, and smoking cessation. The mechanisms of plaque erosion remain poorly understood, and we currently lack validated effective diagnostics or therapeutics for superficial erosion. Eroded plaques have a rich extracellular matrix, an intact fibrous cap, sparse lipid, and few mononuclear cells, but do harbour neutrophil extracellular traps (NETs). We recently reported that NETs amplify and propagate the endothelial damage at the site of arterial lesions that recapitulate …

Titelbild: Stanene‐Based Nanosheets for β‐Elemene Delivery and Ultrasound‐Mediated Combination Cancer Therapy (Angew. Chem. 13/2021) - Chen - 2021 - Angewandte Chemie - Wiley Online Library Skip to Article Content Skip to Article Information Wiley Online Library Wiley Online Library Search within Search term Advanced Search Citation Search Search term Advanced Search Citation Search Login / Register Angewandte Chemie Volume 133, Issue 13 p. 6905-6905 Angewandte Chemie Titelbild Free Access Titelbild: Stanene-Based Nanosheets for β-Elemene Delivery and Ultrasound-Mediated Combination Cancer Therapy (Angew. Chem. 13/2021) Dr. Wei Chen, Dr. Wei Chen Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115 USA These authors contributed equally to this work. Search for more papers by this …

X1 13-( TZ wherein W', W, X, A', X², A², and X3 are as described herein, a payload molecule within the core, and a surface layer comprising a targeting ligand that binds or reacts selectively with a receptor on the outside surface of a cell. Methods of making such nanoparticles, and methods of using such nanoparticles as drug delivery vehicles, are also provided.

CA/siScr, free siPLK1 and PBS groups in Figure 6b, and a TUNEL staining image was inadvertently used for the RBCm-CA/siPLK1 group in Figure 6i. The corrected representative images are now incorporated. This correction does not influence any of the experimental results and conclusions reported in the paper. The authors sincerely apologize to the editors and readers for any inconvenience.

Ultrasound (US)‐mediated sonodynamic therapy (SDT) has emerged as a superior modality for cancer treatment owing to the non‐invasiveness and high tissue‐penetrating depth. However, developing biocompatible nanomaterial‐based sonosensitizers with efficient SDT capability remains challenging. Here, we employed a liquid‐phase exfoliation strategy to obtain a new type of two‐dimensional (2D) stanene‐based nanosheets (SnNSs) with a band gap of 2.3 eV, which is narrower than those of the most extensively studied nano‐sonosensitizers, allowing a more efficient US‐triggered separation of electron (e−)‐hole (h+) pairs for reactive oxygen species (ROS) generation. In addition, we discovered that such SnNSs could also serve as robust near‐infrared (NIR)‐mediated photothermal therapy (PTT) agents owing to their efficient photothermal conversion, and serve as nanocarriers for anticancer drug …

Introduction: Our ~20,000 genes encode over ~1 million protein variants because of alternative splice forms, allelic variation and protein modification. Large-scale genomics studies over the last decade have markedly increased our understanding of cancer biology through analysis of both tissue and biofluids. However, similarly scaled deep and unbiased proteomics studies has been impractical due to the complex workflows required in biofluids. We have previously described Proteograph, a novel platform that leverages the nano-bio interactions of nanoparticles for deep and unbiased proteomic sampling at scale. As proof-of-concept we demonstrated the utility of Proteograph to deeply interrogate the plasma of 141 subjects, 80 healthy controls and 61 early-stage non-small cell lung cancer (NSCLC) subjects, to create a plasma biomarker classifier for the detection of NSCLC versus healthy control with AUC of 0.91 …

Bone defects pose a heavy burden on patients, orthopedic surgeons, and public health resources. Various pathological conditions cause bone defects including trauma, tumors, inflammation, osteoporosis, and so forth. Auto‐ and allograft transplantation have been developed as the most commonly used clinic treatment methods, among which autologous bone grafts are the golden standard. Yet the repair of bone defects, especially large‐volume defects in the geriatric population or those complicated with systemic disease, is still a challenge for regenerative medicine from the clinical perspective. The fast development of biomaterials and nanomedicine favors the emergence and promotion of efficient bone regeneration therapies. In this review, we briefly summarize the progress of novel biomaterial and nanomedical approaches to bone regeneration and then discuss the current challenges that still hinder their …

Introduction: Though early detection of NSCLC greatly improves prognosis, we lack useful clinical tests. Genomics approaches utilizing cell-free DNA provide suitable specificity but moderate sensitivity for early cancer detection. Plasma proteins have the potential to deliver robust panels of biomarkers for early cancer detection that may be complimentary to genomics markers. Complex workflows, which enable deep and unbiased interrogation of plasma proteins that span 10 orders of magnitude, have made it impractical to efficiently perform robust studies, and consequently, comprehensive proteomic data vastly lags other “omics”.Herein, we report a multi-NP Proteograph platform that rapidly, reproducibly, deeply, and scalably interrogates proteins from biofluids. In a study of 268 subjects, comparing on average 1779 plasma proteins of NSCLC subjects to healthy and pulmonary co-morbid controls, we identified …

Diabetes mellitus ist eine lebenslange Stoffwechselerkrankung, die häufige subkutane Insulininjektionen erfordert. Diese Verabreichungsmethode kann jedoch mit Beschwerden des Patienten und einer lokalen Gewebeinfektion verbunden sein. Die orale Verabreichung von Insulin wird aufgrund der wahrscheinlich überlegenen Patientencompliance und ‐bequemlichkeit sowie der Kosteneffizienz als bequemere Methode zur Behandlung von Diabetes verfolgt. Verschiedene biologische Barrieren behindern jedoch die klinische Translation von oralem Insulin. Die rasante Entwicklung der Nanotechnologie im letzten Jahrzehnt bietet vielversprechende Möglichkeiten zur Verbesserung der Bioverfügbarkeit von oralem Insulin. Dieser Kurzaufsatz gibt einen Überblick über biologische Barrieren für die orale Insulinabgabe, fasst wichtige technische Fortschritte zusammen und skizziert zukünftige Perspektiven in oralen …

The delivery of drugs through targeted nanocarriers that are internalized by cells provides an alternative route to diffusion of drugs into cells. Growth factor or vitamin interactions with cancer cells represent a commonly used targeting strategy, as cancer cells often over-express the receptors for nutrition to maintain their fast-growing metabolism. In the case of circulating cancer cells, as in leukaemia and lymphoma, a therapy that targets surface antigens with high affinity and includes a carrier with a long circulating half-life may be the most efficacious. Abraxane is an albumin-bound paclitaxel nanoparticle formulation approved by the Food and Drug Administration in 2005 as a second-line treatment for metastatic breast cancer. The first angiogenesis inhibitor for treating colorectal cancer, Bevacizumab, an anti-VEGF mAb that inhibits the factor responsible for the growth of new blood vessels, was approved in 2004 …

Phosphorus plays an indispensable role in energy metabolism, acid-base balance, and genetic substances transfer. As nanotechnology advances, plenty of phosphorus-based nanomaterials have been developed and widely used in the fields of biology and medicine. The size and structure of phosphorus-based nanomaterials give them unique physicochemical, optical, and biological properties, greatly increasing the variety of nanomedicine. The excellent properties further promote the applications of phosphorus-based nanomaterials in drug nanocarriers, tumor theranostics, biosensors, and bone formation. In this review, we first introduce the phosphorus science to unify current phosphorus-based nanomaterials and discuss their synthesis methods. Furthermore, the representative nanoplatforms utilizing the corresponding properties are highlighted. Finally, research development, potential challenges, and …

The use of photothermal agents (PTAs) in cancer photothermal therapy (PTT) has shown promising results in clinical studies. The rapid degradation of PTAs may address safety concerns but usually limits the photothermal stability required for efficacious treatment. Conversely, PTAs with high photothermal stability usually degrade slowly. The solutions that address the balance between the high photothermal stability and rapid degradation of PTAs are rare. Here, we report that the inherent Cu2+-capturing ability of black phosphorus (BP) can accelerate the degradation of BP, while also enhancing photothermal stability. The incorporation of Cu2+ into BP@Cu nanostructures further enables chemodynamic therapy (CDT)-enhanced PTT. Moreover, by employing 64Cu2+, positron emission tomography (PET) imaging can be achieved for in vivo real-time and quantitative tracking. Therefore, our study not only introduces …

Large-scale, unbiased proteomics studies are constrained by the complexity of the plasma proteome. Here we report a highly parallel protein quantitation platform integrating nanoparticle (NP) protein coronas with liquid chromatography-mass spectrometry for efficient proteomic profiling. A protein corona is a protein layer adsorbed onto NPs upon contact with biofluids. Varying the physicochemical properties of engineered NPs translates to distinct protein corona patterns enabling differential and reproducible interrogation of biological samples, including deep sampling of the plasma proteome. Spike experiments confirm a linear signal response. The median coefficient of variation was 22%. We screened 43 NPs and selected a panel of 5, which detect more than 2,000 proteins from 141 plasma samples using a 96-well automated workflow in a pilot non-small cell lung cancer classification study. Our streamlined …

Diabetes mellitus is a lifelong metabolic disease that requires frequent subcutaneous injections of insulin. However, this method of administration can be associated with patient discomfort and local tissue infection. Oral delivery of insulin has been pursued as a more convenient method for diabetes treatment, given its likely superior patient compliance and convenience as well as cost‐effectiveness. However, various biological barriers hinder the clinical translation of oral insulin. The rapid development of nanotechnology over the last decade offers great promise in improving the bioavailability of oral insulin. This Minireview provides an overview of biological barriers to oral insulin delivery, summarizes significant technological advances, and outlines future perspectives in oral insulin formulations as well as their hypoglycaemic effects.

Introduction: Superficial plaque erosion has emerged as a growing cause of residual thrombotic complications of atherosclerosis in an era of effective lipid lowering, anti-hypertensive therapy, and smoking cessation. The mechanisms of plaque erosion remain poorly understood, and we currently lack validated effective diagnostics or therapeutics for superficial erosion. Lesions complicated by erosion have a rich extracellular matrix, sparse lipid, and few mononuclear cells, but do harbor neutrophil extracellular traps (NETs). We recently reported that NETs amplify and propagate the endothelial damage at the site of arterial lesions that recapitulate in mice elements of superficial erosion. We previously showed that genetic loss of protein arginine deiminase (PAD)-4 function inhibited NETosis and preserved endothelial integrity. Hypothesis: We hypothesized that Col IV-targeted NPs (Col IV-NPs) can deliver PAD4 …

Innate immune cells recognize and respond to pathogen-associated molecular patterns. In particular, polysaccharides found in the microbial cell wall are potent activators of dendritic cells (DCs). Here, we report a new class of nanocapsules, termed sugar-capsules, entirely composed of polysaccharides derived from the microbial cell wall. We show that sugar-capsules with a flexible polysaccharide shell and a hollow core efficiently drain to lymph nodes and activate DCs. In particular, sugar-capsules composed of mannan (Mann-capsule) carrying mRNA (mRNA) promote strong DC activation, mRNA translation, and antigen presentation on DCs. Mann-capsules elicit robust antigen-specific CD4+ and CD8α+ T-cell responses with antitumor efficacy in vivo. The strategy presented in this study is generally applicable for utilizing pathogen-derived molecular patterns for vaccines and immunotherapies.

As a hallmark of solid tumors, hypoxia promotes tumor growth, metastasis, and therapeutic resistance by regulating the expression of hypoxia-related genes. Hypoxia also represents a tumor-specific stimulus that has been exploited for the development of bioreductive prodrugs and advanced drug delivery systems. Cell division cycle 20 (CDC20) functions as an oncogene in tumorigenesis, and we demonstrated the significant upregulation of CDC20 mRNA in the tumor vs paratumor tissues of breast cancer patients and its positive correlation with tumor hypoxia. Herein, a hypoxia-responsive nanoparticle (HRNP) was developed by self-assembly of the 2-nitroimidazole-modified polypeptide and cationic lipid-like compound for delivery of siRNA to specifically target CDC20, a hypoxia-related protumorigenic gene, in breast cancer therapy. The delivery of siCDC20 by HRNPs sufficiently silenced the expression of …

Atherosclerotic lesional macrophages express molecules that promote plaque progression, but lack of mechanisms to therapeutically target these molecules represents a major gap in translational cardiovascular research. Here, we tested the efficacy of a small interfering RNA (siRNA) nanoparticle (NP) platform targeting a plaque-destabilizing macrophage molecule—Ca2+/calmodulin-dependent protein kinase γ (CaMKIIγ). CaMKIIγ becomes activated in advanced human and mouse plaque macrophages and drives plaque necrosis by suppressing the expression of the efferocytosis receptor MerTK. When macrophage-targeted siCamk2g NPs were administered to Western diet–fed Ldlr−/− mice, the atherosclerotic lesions showed decreased CaMKIIγ and increased MerTK expression in macrophages, improved phagocytosis of apoptotic cells (efferocytosis), decreased necrotic core area, and increased fibrous cap …

The ongoing SARS-CoV-2 pandemic highlights the importance of materials science in providing tools and technologies for antiviral research and treatment development. In this Review, we discuss previous efforts in materials science in developing imaging systems and microfluidic devices for the in-depth and real-time investigation of viral structures and transmission, as well as material platforms for the detection of viruses and the delivery of antiviral drugs and vaccines. We highlight the contribution of materials science to the manufacturing of personal protective equipment and to the design of simple, accurate and low-cost virus-detection devices. We then investigate future possibilities of materials science in antiviral research and treatment development, examining the role of materials in antiviral-drug design, including the importance of synthetic material platforms for organoids and organs-on-a-chip, in drug …

ConspectusUnderstanding the interactions between nanomaterials and biological systems plays a pivotal role in enhancing the efficacy of nanomedicine and advancing the disease diagnosis. The nanoparticle–protein corona, an active biomolecular layer, is formed around nanoparticles (NPs) upon mixing with biological fluid. The surface layer which consists of rapidly exchanged biomolecules is called the “soft” corona. The inner layer which is more stable and tightly packed is called the “hard” corona. It has been suggested that the NP–protein corona has a decisive effect on the in vivo fate of nanomedicine upon intravenously administration into the mouse. Furthermore, the features of the NP–protein corona make it a powerful platform to enrich low-abundance proteins from serum/plasma for downstream mass-spectrometry (MS)-based proteomics for biomarker discovery and disease diagnosis.Herein, we …

Nanoparticles containing an aqueous core containing one or more nucleic acids, such as siRNA, and a shell containing one or more hydrophobic cationic materials, one or more amphiphilic materials, and one or more therapeutic, diag nostic, and/or prophylactic agents are. The hydrophobic cationic material and the hydrophobic portion of the amphi philic material provide a non-polar polymer matrix for loading non-polar drugs, protect and promoting siRNA molecule retention inside the NP core, and control drug release. The hydrophilic portion of the amphiphilic material can form a corona around the particle which prolongs circulation of the particles in the blood stream and decreases uptake by the RES.

Structural morphology is the key parameter for efficacy of nanomedicine. To date, lipid‐based nanomaterial has been the most widely used material in nanomedicine and many other biomedical applications. However, to the best of our knowledge, there has not been an in‐depth or systematic investigation of the structure–function relationship of lipid‐based nanostructures. In this report, we investigated the formulation of novel lipid‐based nanostructures via simple tuning of lipid combinations. To prove this concept, we used a combination of various ratios of simple and common phospholipids with different chain lengths (14‐carbon chain DMPC: 6‐carbon chain DHPC) to find out whether a myriad of novel lipid nanostructures could be obtained. Interestingly, many combinations resulted in distinct lipid nanostructures. Drug encapsulation tests confirmed that they are able to load large amounts of drugs for biological …

Provided herein are new compositions including an inactivated pathogen and one or more adjuvant-loaded polymeric nanoparticles, wherein the adjuvant-loaded nanoparticles are bound to the inactivated pathogen. These compositions are useful for preventing and/or treating diseases caused by the specific pathogens, especially when administered to a subject's mucosal membranes.

Introduction: Understanding changes in PPI maps from a healthy and diseased state can illuminate our understanding of biological changes and disease processes. PPI maps enable a higher order of information than a simple listing of components by providing functional context, yet existing maps grossly underrepresent the total biological information potential of PPIs. Herein, we describe Proteograph, a novel platform that leverages the nano-bio interactions of nanoparticles (NPs) for deep and unbiased proteomic sampling that can provide insights on PPI across biological samples. Proteograph leverages the protein corona that forms on the surface of NPs as a function of their distinct biophysicochemical properties. NPs reproducibly bind subsets of proteins from biofluids as a function of protein concentration, protein-NP affinity, and protein-protein interactions to form a corona on the NP surface. We have …

. Oral insulin platforms…… to address various biological barriers are summarized by OC Farokhzad, W. Tao, and co-workers in their Minireview on page19787. Representative advances in facilitating oral insulin delivery are demonstrated, including strategies centered on moieties-mediated transport, cell-penetrating peptide-assisted permeation, smart oral robotics transport, and microenvironment-responsive release.

Methods for making particles, such as nanoparticles, devices useful in the methods, and particles made by the method are described herein. The methods involves the use of micro fluidic device, such that upon mixing solutions of the materials to form the particles (or a solution of the material (Continued) mass fraction of the lipid solution

Black phosphorus (BP)-based nanomaterials have distinguished advantages and potential applications in various biomedical fields. However, their biological effects in physiological systems remain largely unexplored. Here, we systematically revealed a reactive oxygen species (ROS)-mediated mechanism for the selective killing of cancer cells by BP-based nanosheets. The treatment with BP-based materials can induce higher levels of ROS in cancer cells than in normal cells, leading to significant changes in the cytoskeleton, cell cycle arrest, DNA damage, and apoptosis in tumor cell lines. We revealed that the decreased superoxide dismutase activity by lipid peroxides could be an essential mechanism of the selectively higher ROS generation induced by BP-based nanosheets in cancer cells. In addition, the selective killing effect only occurred within a certain dosage range (named “SK range” in this study). Once …

This invention relates to amphiphile-polymer particles, compositions, methods of making, and methods of use thereof.

Introduction: Plasma proteins should be useful biomarkers for disease detection, yet few proteins (~120) are FDA approved. Productive biomarker discovery studies are resource-limited due to the complex biochemical fractionation methods used to address the inherent challenges in unbiased plasma profiling such as the large dynamic range. Herein, we describe Proteograph, a novel platform that leverages the nano-bio interactions of nanoparticles (NPs) for deep and unbiased proteomic sampling. NPs reproducibly bind subsets of proteins from biofluids as a function of protein concentration, protein-NP affinity, and protein-protein interactions to form a corona on the NP surface. The corona composition is directly a function of the NPs' biophysicochemical properties and requires no prior knowledge of the proteins that might be selected by each distinctly engineered NP. With an optimized panel of 10 NPs, we can …

Orale Insulinplattformen zur Durchdringung verschiedener biologischer Barrieren werden im Kurzaufsatz auf S. 19955 von OC Farokhzad, W. Tao et al. diskutiert. Fortschritte beim oralen Insulintransport werden demonstriert, einschließlich Strategien zum zellpenetrierenden peptidunterstützten Transport, zur smarten oralen Robotik und zur mikroumgebungsresponsiven Freisetzung.

This chapter highlights the advances in microfluidic systems that can synthesize libraries of nanoparticles in a well-controlled, reproducible and high-throughput manner. In fact, translation of nanoparticles to the clinic has been slow compared with small-molecule drugs, with the majority of nanoparticles not even reaching the point of in vivo evaluation, and even fewer reaching clinical trials. Amphiphilic molecules such as block copolymers and lipids can self-assemble into nanoparticles when they experience a change in solvent quality. Similarly, inorganic nanoparticles comprising transition metals such as gold, iron and cadmium, among others, undergo self-assembly where metal solutes nucleate, grow and agglomerate into nanoclusters. Nanoparticles exhibiting promising results in vitro are subsequently evaluated in vivo, which is considerably more expensive and resource intensive, especially in non-human …

Germanene (Ge) is a newly discovered two-dimensional (2D) monoelemental material whose biomedical applications remain largely unexplored. Here, we provide the proof-of-principle evidence of a 2D Ge-based strategy for surgical adjuvant treatment. The exfoliated Ge nanosheets (NSs) exhibited high drug-loading capacity, multiresponsive (pH- and near-infrared [NIR]-sensitive) drug-release behavior, NIR-triggered deep tumor penetration, good biocompatibility, and excellent multimodal imaging-guided treatment. When combined with hydrogel (composed of clinically approved agarose and chitosan), the developed drug-loaded Ge@hydrogel was coated on the postoperative wound surface after tumor removal. Followed by NIR irradiation, the generated local hyperthermia and NIR-triggered drug release achieved immediate residual tumor-eliminating and bacteria-killing effects, while the hydrogel served as a …

Combination therapy has been developed as an innovative modality for effective cancer therapy. However, the administration of combinatorial therapeutics is limited by the varying pharmacokinetics of different drugs. Although numerous nanoparticles (NPs) can synchronize the delivery of combinatorial therapeutics to tumor cells, their clinical translation is still challenged, which is partly due to the complexity to precisely control the loading of combinatorial therapeutics to maximize therapeutic efficacy and suboptimal NP properties. Herein, a new redox-responsive polyprodrug nanoplatform was developed for targeted siRNA delivery and synergistic cancer therapy. This NP platform is made with redox-responsive 10-hydroxycamptothecin (HCPT)-based polyprodrug (polyHCPT) as the inner core, amphiphilic lipid-poly (ethylene glycol) (lipid-PEG) as the outer shell, and lactobionic acid (LA) decoration on the surface …