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

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/H(2)O(2)responsive bottlebrush-like unimolecular dextran-POEGMA(9)-b-PMTEMA(22)(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 mu g mL(-1)), and intelligent exogenous ultrasound/endogenous H(2)O(2)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.

Automated summary

The study introduces a tumor-specific and multiple-stimuli responsive nano-riceball for enhanced sono-chemotherapy, featuring high drug loading content and intelligent drug release. Combined sonodynamic therapy and chemotherapy effectively inhibit the growth of hepatocellular carcinoma with minimal side effects.