title: Biodegradable cationic polymeric nanocapsules for overcoming multidrug resistance and enabling drug-gene co-delivery to cancer cells.
abstract: Having unique architectural features, cationic polymeric nanocapsules (NCs) with well-defined covalently stabilized biodegradable structures were generated as potentially universal and safe therapeutic nanocarriers. These NCs were synthesized from allyl-functionalized cationic polylactide (CPLA) by highly efficient UV-induced thiol-ene interfacial cross-linking in transparent miniemulsions. With tunable nanoscopic sizes, negligible cytotoxicity and remarkable degradability, they are able to encapsulate doxorubicin (Dox) with inner cavities and bind interleukin-8 (IL-8) small interfering RNA (siRNA) with cationic shells. The Dox-encapsulated NCs can effectively bypass the P-glycoprotein (Pgp)-mediated multidrug resistance of MCF7/ADR cancer cells, thereby resulting in increased intracellular drug concentration and reduced cell viability. In vitro studies also showed that the NCs loaded with Dox, IL-8 siRNA and both agents can be readily taken up by PC3 prostate cancer cells, resulting in a significant chemotherapeutic effect and/or IL-8 gene silencing.
authors: Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA. ccheng8@buffalo.edu.
authors: Chih-Kuang
authors: CK
authors: Chen
authors: Wing-Cheung
authors: WC
authors: Law
authors: Ravikumar
authors: R
authors: Aalinkeel
authors: Yun
authors: Y
authors: Yu
authors: Bindukumar
authors: B
authors: Nair
authors: Jincheng
authors: J
authors: Wu
authors: Supriya
authors: S
authors: Mahajan
authors: Jessica L
authors: JL
authors: Reynolds
authors: Yukun
authors: Y
authors: Li
authors: Cheng Kee
authors: CK
authors: Lai
authors: Emmanuel S
authors: ES
authors: Tzanakakis
authors: Stanley A
authors: SA
authors: Schwartz
authors: Paras N
authors: PN
authors: Prasad
authors: Chong
authors: C
authors: Cheng
mesh_terms: D001672:Biocompatible Materials; D002412:Cations; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016209:Interleukin-8 / Q000737:chemistry; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D053769:Nanocapsules / Q000737:chemistry*; D053758:Nanoparticles; D036103:Nanotechnology; D009369:Neoplasms / Q000188:drug therapy* / Q000628:therapy*; D011091:Polyesters / Q000737:chemistry; D034741:RNA, Small Interfering / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D001672:Biocompatible Materials; D002412:Cations; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D016209:Interleukin-8; D053769:Nanocapsules; D011091:Polyesters; D034741:RNA, Small Interfering; C033616:poly(lactide); D004317:Doxorubicin