A ‘two-in-one’ tumor-specific-hydrogel-assisted strategy for intravesical chemotherapy and protection of normal tissues

Intravesical therapy is commonly administered after transurethral resection to treat bladder cancer, but it frequently induces chemical cystitis as a side effect. To address this issue, we propose a 'two-in-one' strategy designed to simultaneously enable intravesical chemotherapy and protect normal bladder tissues. A tumor-specific hydrogel serves as a size‑selective filter that excludes entities larger than its pore size, while ensuring sustained and unsaturated drug action. Cell membrane‑derived nanovesicles of tailored sizes were prepared to deliver cytotoxic or protective agents, respectively. Leveraging their homologous targeting ability and competitive diffusion‑enhanced redistribution, these nanovesicles selectively shuttle their cargoes to the intended sites of action. This multifaceted mechanism significantly enhances tumor‑to‑normal tissue selectivity, resulting in 98% tumor inhibition while reducing the incidence of inflammation in normal urothelium by 97%.