Controllable Regulation of Ag 2 S Quantum Dots-Mediated Protein Nanoassemblies for Imaging-Guided Synergistic PDT/PTT/Chemotherapy Against Hypoxic Tumor.

The combination of phototherapy and chemotherapy holds great potential for cancer treatment, while hypoxia in tumor as well as unexpected drug release largely restrict anticancer therapy. Inspired by the natural intelligence, herein we present for the first time a "bottom-up" protein self-assembly strategy mediated by NIR quantum dots (QDs) with multicharged electrostatic interactions to develop a tumor microenvironment (TME)-responsive theranostic nanoplatform for imaging-guided synergistic PDT/PTT/chemotherapy. Catalase (CAT) possesses diverse surface charge distribution under different pH conditions. After modification by Ce6, the formulated CAT-Ce6 with patchy negative charges can be assembled with NIR Ag2 S QDs by regulating their electrostatic interactions, allowing for effective incorporation of specific anticancer drug oxaliplatin (Oxa). Such Ag2 S@CAT-Ce6@Oxa nanosystems are able to visualize nanoparticle accumulation to guide the subsequent phototherapy, together with significant alleviation of tumor hypoxia to further enhance PDT. Moreover, the acidic TME triggers controllable disassembly through weakening the CAT surface charge to disrupt electrostatic interactions in assemblies, allowing for sustained drug release. Both in vitro and in vivo results demonstrate remarkable inhibition of colorectal tumor growth with a synergistic effect. Overall, this multicharged electrostatic protein self-assembly strategy provides a versatile platform for realizing TME-specific theranostics with high efficiency and safety, promising for clinical translation. This article is protected by copyright. All rights reserved.