TY - JOUR
T1 - Biodegradable cationic polymeric nanocapsules for overcoming multidrug resistance and enabling drug-gene co-delivery to cancer cells
AU - Chen, Chih Kuang
AU - Law, Wing Cheung
AU - Aalinkeel, Ravikumar
AU - Yu, Yun
AU - Nair, Bindukumar
AU - Wu, Jincheng
AU - Mahajan, Supriya
AU - Reynolds, Jessica L.
AU - Li, Yukun
AU - Lai, Cheng Kee
AU - Tzanakakis, Emmanuel S.
AU - Schwartz, Stanley A.
AU - Prasad, Paras N.
AU - Cheng, Chong
PY - 2014/2/7
Y1 - 2014/2/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84892667514&partnerID=8YFLogxK
U2 - 10.1039/c3nr04804g
DO - 10.1039/c3nr04804g
M3 - Journal article
C2 - 24326457
SN - 2040-3364
VL - 6
SP - 1567
EP - 1572
JO - Nanoscale
JF - Nanoscale
IS - 3
ER -
