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. 2021 Mar;5(3):e2000416.
doi: 10.1002/smtd.202000416. Epub 2020 Sep 2.

Multi-Responsive Bottlebrush-Like Unimolecules Self-Assembled Nano-Riceball for Synergistic Sono-Chemotherapy

Xiaoxiao Shi  1 , Yang Zhang  1 , Ye Tian  1 , Shuyu Xu  1 , En Ren  1 , Shuang Bai  1 , Xiaoyuan Chen  2 , Chengchao Chu  1 , Zhigang Xu  3 , Gang Liu  1
Affiliations

Multi-Responsive Bottlebrush-Like Unimolecules Self-Assembled Nano-Riceball for Synergistic Sono-Chemotherapy

Xiaoxiao Shi et al. Small Methods. 2021 Mar.

Abstract

Improved drug loading content, bioavailability, and controlled release in targeted tissue have been major bottlenecks in the design of precision nanomedicine. Herein, a tumor-specific and multiple-stimuli responsive nano-riceball is proposed and validated for enhanced sono-chemotherapy. The nano-riceball (NGR@DDP) possesses a well-designed core-shell structure, formed by an inner core assembly that contains ultrasound/H2 O2 responsive bottlebrush-like unimolecular dextran-POEGMA9 -b-PMTEMA22 (DOS) with co-loaded doxorubicin and Purpurin 18. This inner core of NGR@DDP is further buried by a "striffen" of NGR (Asn-Gly-Arg)-modified RBC-membrane derived from CRISPR-engineered mice. As a result, nano-riceball NGR@DDP is featured with high drug stuffing content (30.3 wt%), low critical micelle concentration (5.93 µg mL-1 ), and intelligent exogenous ultrasound/endogenous H2 O2 stimuli-triggered precise drug release at tumor site. Under fluorescence/photoacoustic imaging guidance, combined sonodynamic therapy and chemotherapy exhibit excellent synergistic effect, and dramatically inhibit the growth of orthotopic HepG2 hepatocellular carcinoma with negligible side effects. This nano-riceball strategy provides a facile way to achieve function hybridization for personalized nanomedicine.

Keywords: multi-responsive molecules; polymeric micelles; sono-chemotherapy; targeted therapy; theranostics.

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