title: Photoinduced Mild Hyperthermia and Synergistic Chemotherapy by One-Pot-Synthesized Docetaxel-Loaded Poly(lactic-co-glycolic acid)/Polypyrrole Nanocomposites.
abstract: Mild hyperthermia has shown great advantages when combined with chemotherapy. The development of a multifunctional platform for the integration of mild hyperthermia capability into a drug-loading system is a key issue for cancer multimodality treatment application. Herein, a facile one-pot in situ fabrication protocol of docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA)/polypyrrole (PPy) nanocomposites was developed. While the PLGA nanoparticles (NPs) allow efficient drug loading, the PPy nanobulges embedded within the surface of the PLGA NPs, formed by in situ pyrrole polymerization without the introduction of other template agents, can act as ideal mediators for photoinduced mild hyperthermia. Physiochemical characterizations of the as-prepared nanocomposites, including structure, morphology, photothermal effects, and an in vitro drug release profile, were systematically investigated. Further, 2-deoxyglucose-terminated poly(ethylene glycol) (PEG) was anchored onto the surface of the nanocomposites to endow the nanoplatform with targeting ability to tumor cells, which resulted in a 17-fold increase of NP internalization within human breast cancer cells (MCF-7) as competed with PEG-modified nanocomposites. Mild hyperthermia can be successfully mediated by the nanoplatform, and the temperature can be conveniently controlled by careful modulation of the PPy contents within the nanocomposites or the laser power density. Importantly, we have demonstrated that MCF-7 cells, which are markedly resistant to heat treatment of traditional water-bath hyperthermia, became sensitive to the PLGA/PPy nanocomposite-mediated photothermal therapy under the same mild-temperature hyperthermia. Moreover, DTX-loaded PLGA/PPy-nanocomposite-induced mild hyperthermia can strongly enhance drug cytotoxicity to MCF-7 cells. Under the same thermal dose, photoinduced hyperthermia can convert the interaction between hyperthermia and drug treatment from interference to synergism. This is the first report on the one-pot synthesis of PLGA/PPy nanocomposites by in situ pyrrole polymerization, and such a multifunctional nanoplatform is demonstrated as a high-potential agent for photoinduced mild hyperthermia and enhanced chemotherapy.
authors: State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, ‡Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, and §Department of Chemistry, Center for Frontier Polymer Research, Tsinghua University , Beijing 100084, P. R. China.
authors: Jie
authors: J
authors: Yuan
authors: State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, ‡Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, and §Department of Chemistry, Center for Frontier Polymer Research, Tsinghua University , Beijing 100084, P. R. China.
authors: Jialu
authors: J
authors: Liu
authors: State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, ‡Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, and §Department of Chemistry, Center for Frontier Polymer Research, Tsinghua University , Beijing 100084, P. R. China.
authors: Qi
authors: Q
authors: Song
authors: State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, ‡Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, and §Department of Chemistry, Center for Frontier Polymer Research, Tsinghua University , Beijing 100084, P. R. China.
authors: Dan
authors: D
authors: Wang
authors: State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, ‡Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, and §Department of Chemistry, Center for Frontier Polymer Research, Tsinghua University , Beijing 100084, P. R. China.
authors: Wensheng
authors: W
authors: Xie
authors: State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, ‡Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, and §Department of Chemistry, Center for Frontier Polymer Research, Tsinghua University , Beijing 100084, P. R. China.
authors: Hao
authors: H
authors: Yan
authors: State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, ‡Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, and §Department of Chemistry, Center for Frontier Polymer Research, Tsinghua University , Beijing 100084, P. R. China.
authors: Junfeng
authors: J
authors: Zhou
authors: State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, ‡Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, and §Department of Chemistry, Center for Frontier Polymer Research, Tsinghua University , Beijing 100084, P. R. China.
authors: Yen
authors: Y
authors: Wei
authors: State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, ‡Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, and §Department of Chemistry, Center for Frontier Polymer Research, Tsinghua University , Beijing 100084, P. R. China.
authors: Xiaodan
authors: X
authors: Sun
authors: State Key Laboratory of New Ceramics and Fine Processing, School of Materials Science and Engineering, ‡Key Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, and §Department of Chemistry, Center for Frontier Polymer Research, Tsinghua University , Beijing 100084, P. R. China.
authors: Lingyun
authors: L
authors: Zhao
mesh_terms: D000970:Antineoplastic Agents; D000077143:Docetaxel; D006801:Humans; D006979:Hyperthermia, Induced; D019344:Lactic Acid; D053761:Nanocomposites; D053758:Nanoparticles; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011758:Pyrroles; D043823:Taxoids
chemical_list: D000970:Antineoplastic Agents; D011108:Polymers; D011758:Pyrroles; D043823:Taxoids; D000077143:Docetaxel; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; C067635:polypyrrole; D019344:Lactic Acid
keywords: NIR thermotherapy; PLGA/PPy nanocomposites; docetaxel; mild-temperature hyperthermia; multifunctional nanoplatform