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Imaging of nanotherapeutic drug action

纳米治疗药物作用的成像

基本信息

批准号：
9261150
负责人：
RALPH WEISSLEDER, MD, PHD
金额：
$ 58.57万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-03-23 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9261150
关键词：
2,4-Dinitrophenol Abraxane Address Affinity Albumin-Stabilized Nanoparticle Paclitaxel Anatomy Biological Cell Death Cells Chemicals Clinic Clinical Clinical Data Clinical Trials DNA Damage Data Development Drug Kinetics Drug effect disorder FDA approved Feasibility Studies Folic Acid Future Goals Heterogeneity Histopathology Human Image Image Analysis Imaging technology Immunocompetent In Vitro Label Ligands Magnetic Resonance Imaging Magnetic nanoparticles Malignant Neoplasms Malignant neoplasm of ovary Measures Mediating Methods Mitotic Modeling Mus Myeloid Cells Myeloproliferative disease Nanotechnology Paclitaxel Patients Peritoneum Permeability Phagocytes Pharmaceutical Preparations Pharmacodynamics Pharmacology Play Population Preparation Progression-Free Survivals Resistance Role Testing Therapeutic Time Toxic effect Work Xenograft procedure base cancer cell cell killing cell type design experimental study improved in vivo in vivo imaging innovation insight interest intravital microscopy macrophage member molecular diagnostics mouse model nanoencapsulated nanoformulation nanomaterials nanoparticle nanotherapeutic neoplastic cell novel therapeutics predictive of treatment response responders and non-responders response subcutaneous treatment response tumor

项目摘要

Well over a thousand patients have now received chemically distinct, nano-encapsulated chemotherapeutics, generally showing lower toxicity, increased tumoral accumulation of payloads and occasionally improved progression free survival. Experimentally, an even larger number of new constructs and approaches have been pioneered by Nanotechnology Alliance members and other groups. Testing in mice usually involves measuring tumor sizes, survival or the use of histopathology and other molecular diagnostics. Yet, despite these advances, much less is known on how these nanomaterials actually work or fail in vivo, what the spatial and temporal heterogeneity is and how efficacy can be improved. Armed with new biological insight from recent feasibility studies leading to this application (Sci Transl Med, 2015;7,314ra183; Nat Comm 2015;6,8692) and the recent developments of new in vivo imaging technologies (Nat Commun 2013;4,1504; PLoS One 2013;8:e60988; Nat Methods. 2015;12:577-585; ChemMedChem 2014;9:1131-5) we are now able to address these important cancer nanotechnology questions in ways that were not previously possible. The goal of this project is to perform imaging analyses of therapeutic nanoparticles, addressing key questions on nanoparticle distribution (pharmacokinetics, PK) and cellular response (pharmacodynamics, PD): i) why aren't current clinical TNP more efficient (aim 1); ii) how much does tumor targeting with affinity ligands help to improve efficacy (aim 2) and iii) can we select responders from non-responders by nanoparticle enhanced MR imaging (aim 3)? We hypothesize that a considerable proportion of tumor cell accumulation is mediated by tumoral myeloid cells (macrophages) rather than by cancer cells, offering a new strategy to further enhance efficacy. To the best of our knowledge, this project is complementary to existing Alliance projects and will be useful to other Alliance members across the consortium through future interactions. It will also provide a much needed biological understanding of nanoparticle enhanced MR imaging findings to interpret clinical data.

现在已经有一千多名患者接受了化学上不同的纳米封装化疗药物，