title: Enhanced in vivo antitumor efficacy of dual-functional peptide-modified docetaxel nanoparticles through tumor targeting and Hsp90 inhibition.
abstract: Although conventional anticancer drugs exhibit excellent efficacy, serious adverse effects and/or even toxicity have occurred due to their nonselectivity. Moreover, active targeting approaches have not consistently led to successful outcomes. Ligands that simultaneously possess targeting capability and exert a strong influence on intracellular signaling cascades may be expected to improve the therapeutic efficacy of active targeting nanoparticulate carriers. In this study, we screened a targeting peptide, LPLTPLP, which specifically bound to non-small cell lung cancer (NSCLC) specimens in vitro. Surprisingly, this peptide inhibited the expression of Hsp90 and induced apoptosis by preventing autophagy in A549 cells treated with docetaxel. The results suggested that this peptide might be used as a promising dual-functional ligand for cancer treatment. Based on these findings, we designed and developed a novel active targeting delivery system by modifying docetaxel nanoparticles (DNP) with the dual-functional ligand LPLTPLP. We consistently demonstrated that the cellular uptake of nanoparticles (NPs) was significantly enhanced in vitro. Furthermore, the targeting NPs exhibited significantly improved antitumor efficacy and biodistribution compared with nontargeting nanodrug and free docetaxel. These findings demonstrate the feasibility of dual-functional NPs for efficient anticancer therapy.
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Huifeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Chunying
authors.initials: C
authors.lastname: Hou
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ji
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China. Electronic address: liuyanyong@126.com.
authors.forename: Yanyong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing, China. Electronic address: pingping_zuo@126.com.
authors.forename: Pingping
authors.initials: P
authors.lastname: Zuo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D041702:BALB 3T3 Cells; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010455:Peptides / Q000737:chemistry*; D043823:Taxoids / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D018841:HSP90 Heat-Shock Proteins; D010455:Peptides; D043823:Taxoids; D000077143:Docetaxel
keywords: Heat shock protein 90; Lung cancer; Nanoparticles; Targeting peptide; Targeting therapy