TARGETED POLYMERIC NANOPARTICLES FOR CANCER THERAPY

$614,343U54FY2009CANIH

Massachusetts Institute Of Technology, Cambridge MA

Investigators

Linked publications & trials

Paper 30500466 Paper 28193901 Paper 27792877 Paper 27098438 Paper 26490455 Paper 26267184 Paper 26258867 Paper 26102604 Paper 26098019 Paper 26089520 Paper 25985456 Paper 25650428 Paper 25289021 Paper 25230005 Paper 25221434 Paper 25214538 Paper 25119520 Paper 24932403 Paper 24887807 Paper 24824296 Paper 24220635 Paper 24177171 Paper 23969105 Paper 23835814 Paper 23832121 Paper 23808626 Paper 23713956 Paper 23697579 Paper 23656279 Paper 23377294 Paper 23339821 Paper 23225635 Paper 23042209 Paper 22983492 Paper 22909216 Paper 22896676 Paper 22764208 Paper 22762250 Paper 22584163 Paper 22408498 Paper 22376183 Paper 22337601 Paper 22272219 Paper 22268625 Paper 22201893 Paper 22185195 Paper 22113800 Paper 22020333 Paper 21987724 Paper 21981330 Paper 21977404 Paper 21888516 Paper 21780311 Paper 21685903 Paper 21547317 Paper 21495138 Paper 21433105 Paper 21346169 Paper 21317907 Paper 21245339 Paper 21233423 Paper 21187397 Paper 21123946 Paper 20949198 Paper 20921363 Paper 20886481 Paper 20859943 Paper 20836539 Paper 20814923 Paper 20726522 Paper 20689678 Paper 20677297 Paper 20625581 Paper 20625468 Paper 20518524 Paper 20481508 Paper 20394530 Paper 20387142 Paper 20336708 Paper 20231381 Paper 20228787 Paper 20217810 Paper 20217526 Paper 20174478 Paper 20166699 Paper 20148638 Paper 20133865 Paper 20080556 Paper 20028085 Paper 20025223 Paper 20025222 Paper 20025010 Paper 20023731 Paper 19893516 Paper 19850333 Paper 19812695 Paper 19801750 Paper 19713582 Paper 19697933 Paper 19675897

Abstract

With advances in nanotechnology, it is now possible to develop highly selective and effective cancer therapeutics by combining specialized biomaterials with currently available chemotherapeutic agents. The aim of project 1 of this U54 proposal is to develop technologies for in vivo targeted delivery of cytotoxic drug encapsulated controlled release polymer nanoparticles to cancer cells. This could allow for a large amount of drug to be delivered to cancer cells and make it possible to reach a steady state cytotoxic drug concentration at the tumor site over an extended period of time. The combination of targeted delivery and controlled release could also decrease the likelihood of significant systemic toxicity since the drug is encapsulated and biologically unavailable during transit in systemic circulation. We will build upon our previous research on long circulating nanoparticles as published in Science and engineer biocompatible and biodegradable nanoparticles and optimize these for targeted drug delivery to cancer cells. By using high throughput combinatorial methods, we will develop a library of more than 3000 targeted nanoparticle formulations and optimize multiple parameters including, size, chemical structure and charge of nanoparticles;and density of targeting molecules on the nanoparticle surface for targeted delivery. As a model targeting molecule, we will use nuclease resistant RNA ligands that bind to tumor-antigens on the surface of prostate cancer cells. By isolating a panel of RNA ligands that bind to prostate tumor epitopes, we propose to develop polyvalent targeted nanoparticles that may overcome tumor heterogeneity which in some cases has hindered the clinical translation of previous targeted approaches. We believe this project has broad significance, since the successful development of this technology may result in the development of the next generation of nanoscale cancer therapeutic modalities.

View original record on NIH RePORTER →