Synthesis of a Pillar[5]arene-Based Polyrotaxane for Enhancing the Drug Loading Capacity of PCL-Based Supramolecular Amphiphile as an Excellent Drug Delivery Platform

• Published in: Biomacromolecules 2018-07, Vol.19 (7), p.2923-2930
• Main Authors: He, Jianping, Chen, Jianzhuang, Lin, Shaoliang, Niu, Dechao, Hao, Jina, Jia, Xiaobo, Li, Nan, Gu, Jinlou, Li, Yongsheng, Shi, Jianlin
• Format: Article
• Language: English
• Subjects: Acrylic Resins - chemistry; Adamantane - analogs & derivatives; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; beta-Cyclodextrins - chemistry; Caproates - chemistry; Cell Line, Tumor; Doxorubicin - administration & dosage; Doxorubicin - pharmacokinetics; Lactones - chemistry; Mice; Mice, Inbred BALB C; Nanoconjugates - chemistry; Rotaxanes - chemistry; Surface-Active Agents - chemical synthesis
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/acs.biomac.8b00488

A pillar[5]­arene-based nonionic polyrotaxane (PR) with star-poly­(ε-caprolactone) (S-PCL) as the axle, pillar[5]­arene (DEP5) as the wheel and adamantane as the end-capped group is designed and synthesized. The resulting PR is subsequently assembled with β-cyclodextrin end-capped pH-stimulated poly­(acrylic acid) (CD-PAA) via a host–guest interaction to form the supramolecular pseudoblock polymer PR-PAA. This supramolecular pseudoblock polymer could self-assemble in aqueous solution to produce PR-PAA-based supramolecular vesicular nanoparticles (PR-SVNPs), which present significantly enhanced drug loading capacity (DLC, 45.6%) of DOX, much higher than those of superamphiphiles (PCL-PAA, 17.1%). Such a high DLC of PR-SVNPs can be most probably attributed to the greatly decreased crystallinity of PCL in PR. Moreover, the loaded drugs could be selectively released in an acidic microenvironment-responsive manner. Compared to free DOX, the DOX-loaded PR-SVNPs (DOX@PR-SVNPs) shows much enhanced cellular uptake and cytotoxicity against the SMMC-7721. More importantly, thanks to the enhanced permeability and retention (EPR) effect, DOX@PR-SVNPs exhibits appealing features such as extremely low toxicity, highly efficient intratumoral accumulation and substantial antitumor efficacy in vivo.