Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers Export

@article{citeulike:2525982, abstract = {There has been progressively heightened interest in the development of targeted nanoparticles (NPs) for differential delivery and controlled release of drugs. Despite nearly three decades of research, approaches to reproducibly formulate targeted NPs with the optimal biophysicochemical properties have remained elusive. A central challenge has been defining the optimal interplay of parameters that confer molecular targeting, immune evasion, and drug release to overcome the physiological barriers in vivo. Here, we report a strategy for narrowly changing the biophysicochemical properties of NPs in a reproducible manner, thereby enabling systematic screening of optimally formulated drug-encapsulated targeted NPs. NPs were formulated by the self-assembly of an amphiphilic triblock copolymer composed of end-to-end linkage of poly(lactic-co-glycolic-acid) (PLGA), polyethyleneglycol (PEG), and the A10 aptamer (Apt), which binds to the prostate-specific membrane antigen (PSMA) on the surface of prostate cancer (PCa) cells, enabling, respectively, controlled drug release, "stealth" properties for immune evasion, and cell-specific targeting. Fine-tuning of NP size and drug release kinetics was further accomplished by controlling the copolymer composition. By using distinct ratios of PLGA-b-PEG-b-Apt triblock copolymer with PLGA-b-PEG diblock copolymer lacking the A10 Apt, we developed a series of targeted NPs with increasing Apt densities that inversely affected the amount of PEG exposure on NP surface and identified the narrow range of Apt density when the NPs were maximally targeted and maximally stealth, resulting in most efficient PCa cell uptake in vitro and in vivo. This approach may contribute to further development of targeted NPs as highly selective and effective therapeutic modalities. 10.1073/pnas.0711714105}, author = {Gu, Frank and Zhang, Liangfang and Teply, Benjamin A. and Mann, Nina and Wang, Andrew and Radovic-Moreno, Aleksandar F. and Langer, Robert and Farokhzad, Omid C.}, citeulike-article-id = {2525982}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0711714105}, citeulike-linkout-1 = {http://www.pnas.org/cgi/content/abstract/105/7/2586}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18272481}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18272481}, day = {19}, doi = {10.1073/pnas.0711714105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {amphiphilic-triblock-copolymer, aptamer, ccne-grant, cellular-delivery, docetaxel, endocytosis, fluorescent-microscopy, mit-mgh-ccne, murine-model, polymer-nanoparticle, tumor}, month = {February}, number = {7}, pages = {2586--2591}, posted-at = {2008-03-13 14:55:05}, priority = {2}, title = {Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers}, url = {http://dx.doi.org/10.1073/pnas.0711714105}, volume = {105}, year = {2008} }

TY - JOUR ID - citeulike:2525982 L3 - citeulike-article-id:2525982 N2 - There has been progressively heightened interest in the development of targeted nanoparticles (NPs) for differential delivery and controlled release of drugs. Despite nearly three decades of research, approaches to reproducibly formulate targeted NPs with the optimal biophysicochemical properties have remained elusive. A central challenge has been defining the optimal interplay of parameters that confer molecular targeting, immune evasion, and drug release to overcome the physiological barriers in vivo. Here, we report a strategy for narrowly changing the biophysicochemical properties of NPs in a reproducible manner, thereby enabling systematic screening of optimally formulated drug-encapsulated targeted NPs. NPs were formulated by the self-assembly of an amphiphilic triblock copolymer composed of end-to-end linkage of poly(lactic-co-glycolic-acid) (PLGA), polyethyleneglycol (PEG), and the A10 aptamer (Apt), which binds to the prostate-specific membrane antigen (PSMA) on the surface of prostate cancer (PCa) cells, enabling, respectively, controlled drug release, "stealth" properties for immune evasion, and cell-specific targeting. Fine-tuning of NP size and drug release kinetics was further accomplished by controlling the copolymer composition. By using distinct ratios of PLGA-b-PEG-b-Apt triblock copolymer with PLGA-b-PEG diblock copolymer lacking the A10 Apt, we developed a series of targeted NPs with increasing Apt densities that inversely affected the amount of PEG exposure on NP surface and identified the narrow range of Apt density when the NPs were maximally targeted and maximally stealth, resulting in most efficient PCa cell uptake in vitro and in vivo. This approach may contribute to further development of targeted NPs as highly selective and effective therapeutic modalities. 10.1073/pnas.0711714105 IS - 7 JF - Proceedings of the National Academy of Sciences EP - 2591 TI - Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers VL - 105 SP - 2586 KW - amphiphilic-triblock-copolymer KW - aptamer KW - ccne-grant KW - cellular-delivery KW - docetaxel KW - endocytosis KW - fluorescent-microscopy KW - mit-mgh-ccne KW - murine-model KW - polymer-nanoparticle KW - tumor AU - Gu, Frank AU - Zhang, Liangfang AU - Teply, Benjamin AU - Mann, Nina AU - Wang, Andrew AU - Radovic-Moreno, Aleksandar AU - Langer, Robert AU - Farokhzad, Omid PY - 2008/02/19/ UR - http://dx.doi.org/10.1073/pnas.0711714105 ER -