title: Aptamer-mediated delivery of docetaxel to prostate cancer through polymeric nanoparticles for enhancement of antitumor efficacy.
abstract: Treatment of aggressive prostate cancer remains a great challenge due to inadequate drug distribution into the cancerous lesions after administration. This study aimed to develop aptamer-anchored nanoparticles (apt-NPs) for systemic delivery of docetaxel (DTX) and to evaluate the tumoricidal activity against the prostate cancer in vitro and in vivo. DTX-loaded apt-NPs (DTX-apt-NPs) were prepared by a solvent diffusion technique using functional PLGA-b-PEG and sodium oleate. DTX-apt-NPs were characterized by in vitro release, antitumor activity, cellular uptake and cytotoxic mechanisms. Pharmacokinetics and tissue distribution studies were performed in rats to investigate the biofate of DTX-apt-NPs. Finally, the in vivo antitumor efficacy was examined on the LNCaP cells xenograft tumor model. The resulting DTX-apt-NPs were 93.6nm in particle size with narrow distribution and possessed a high entrapment efficiency (97.62%) and acceptable drug loading (8.91%). DTX-apt-NPs demonstrated an enhanced in vitro antitumor effect and marked cellular uptake compared with the solution formulation or conventional nanoparticles. The intracellular trafficking of DTX-apt-NPs was shown to be an active transport process involving the clathrin-dependent endocytosis. Anti-PSMA aptamer-mediated delivery was assumed mainly responsible for the enhanced antitumor efficacy. DTX-apt-NPs that can target to PSMA-overexpressed prostate cancer provide a feasible approach for systemic delivery of DTX to the cancerous prostate to achieve a fine prognosis.
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China; Department of Pharmaceutics, Shanghai Dermatology Hospital, Shanghai 200443, PR China.
authors.forename: Zhongjian
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Zongguang
authors.initials: Z
authors.lastname: Tai
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Fenfen
authors.initials: F
authors.lastname: Gu
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Chuling
authors.initials: C
authors.lastname: Hu
authors.affiliation: Pharmaceutical Research Laboratory, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, PR China. Electronic address: qgzhu@126.com.
authors.forename: Quangang
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai 200433, PR China. Electronic address: liullk@126.com.
authors.forename: Shen
authors.initials: S
authors.lastname: Gao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004337:Drug Carriers; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D052157:Aptamers, Nucleotide; D004337:Drug Carriers; D043823:Taxoids; D000077143:Docetaxel
keywords: Antitumor efficacy; Aptamer; Docetaxel; Prostate cancer; Prostate specific membrane antigen (PSMA); Targeted drug delivery