Tumor-specific penetrating peptides-functionalized hyaluronic acid- d -α-tocopheryl succinate based nanoparticles for multi-task delivery to invasive cancers

• Published in: Biomaterials 2015-12, Vol.71, p.11-23
• Main Authors: Liang, De-Sheng, Su, Hai-Tao, Liu, Yu-Jie, Wang, Ai-Ting, Qi, Xian-Rong
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; alpha-Tocopherol - chemistry; Animals; Antineoplastic Agents - administration & dosage; Biocompatibility; Biomedical materials; Cancer; Cell Line, Tumor; Dentistry; Drug delivery systems; Humans; Hyaluronic Acid - chemistry; In vivo tests; Male; Mice; Mice, Inbred BALB C; Nanoparticles; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Outerwear; Peptides - chemistry; Peptides - metabolism; Surgical implants; Tumors
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2015.08.035

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.