title: Tumor-specific penetrating peptides-functionalized hyaluronic acid-d-α-tocopheryl succinate based nanoparticles for multi-task delivery to invasive cancers.
abstract: Poor site-specific delivery and incapable deep-penetration into tumor are the intrinsic limitations to successful chemotherapy. Here, the tumor-homing penetrating peptide tLyP-1-functionalized nanoparticles (tLPTS/HATS NPs), composed of two modularized amphiphilic conjugates of tLyP-1-PEG-TOS (tLPTS) and TOS-grafted hyaluronic acid (HATS), had been fabricated for tumor-targeted delivery of docetaxel (DTX). The prepared tLPTS/HATS NPs had about 110 nm in mean diameter, high drug encapsulation efficiency (93%), and sustained drug release behavior. In vitro studies demonstrated that the tLPTS/HATS NPs exhibited enhanced intracellular delivery and much better anti-invasion ability, cytotoxicity, and apoptosis against both invasive PC-3 and MDA-MB-231 cells as compared to the non-tLyP-1-functionalized HATS NPs. The remarkable penetrability and inhibitory effect on both PC-3 and MDA-MB-231 multicellular tumor spheroids were also identified for the tLPTS/HATS NPs. In vivo biodistribution imaging demonstrated the tLPTS/HATS NPs possessed much more lasting accumulation and extensive distribution throughout tumor regions than the HATS NPs. The higher in vivo therapeutic efficacy with lower systemic toxicity of the tLPTS/HATS NPs was also verified by the PC-3 xenograft model in athymic nude mice. These results suggested that the designed novel tLPTS/HATS NPs were endowed with tumor recognition, internalization, penetration, and anti-invasion, and thus might be a promising anticancer drug delivery vehicle for targeted cancer therapy.
authors: School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, PR China; Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, 38 Xueyuan Road, Haidian District, Beijing 100191, PR China.
authors: De-Sheng
authors: DS
authors: Liang
authors: School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, PR China; Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, 38 Xueyuan Road, Haidian District, Beijing 100191, PR China.
authors: Hai-Tao
authors: HT
authors: Su
authors: School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, PR China; Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, 38 Xueyuan Road, Haidian District, Beijing 100191, PR China.
authors: Yu-Jie
authors: YJ
authors: Liu
authors: School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, PR China; Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, 38 Xueyuan Road, Haidian District, Beijing 100191, PR China.
authors: Ai-Ting
authors: AT
authors: Wang
authors: School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, PR China; Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, 38 Xueyuan Road, Haidian District, Beijing 100191, PR China; State Key Laboratory of Natural and Biomimetic Drugs, 38 Xueyuan Road, Haidian District, Beijing 100191, PR China. Electronic address: qixr@bjmu.edu.cn.
authors: Xian-Rong
authors: XR
authors: Qi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D024502:alpha-Tocopherol / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D010455:Peptides; D006820:Hyaluronic Acid; D024502:alpha-Tocopherol
keywords: CD44 receptor; NRP-1 receptor; Site-specific delivery; Tumor-homing penetrating peptide tLyP-1; d-α-tocopheryl succinate (TOS)