期刊
BIOMACROMOLECULES
卷 19, 期 7, 页码 2923-2930出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.biomac.8b00488
关键词
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资金
- National Natural Science Foundation of China [51621002]
- National Key Research and Development Program of China [2016YFA0203700]
- NSFC [51572083, 51461165202, 51472085]
- Program of Shanghai Academic/Technology Research Leader [18XD1401400]
- Basic Research Program of Shanghai [17JC1404702]
- Shanghai Rising-Star Program [16QA1401300]
- 111 Project [B14018]
- Fundamental Research Funds for Central Universities [222201718002]
A pillar[5]arene-based nonionic polyrotaxane (PR) with star-poly(e-caprolactone) (S-PCL) as the axle, pillar[5]arene (DEPS) as the wheel and adamantane as the end-capped group is designed and synthesized. The resulting PR is subsequently assembled with beta-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.
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