Enhanced Penetration and Retention of CuS‐Based Nanosystem Through NIR Light and In Situ Enzyme Response for Improved Tumor Therapy

Abstract The efficient way to increase the therapeutic efficacy of nanomedicines is by encouraging the penetration and enhancing the retention of nanoparticles at the tumor site. However, it is a serious dilemma that small nanoparticles can penetrate deep into the tumor tissue but easily be cleared into the surrounding tissues. In order to solve this dilemma, a smart nanosystem is created to address this problem, ensuring both the effective penetration of tiny nanoparticles (NPs) and their appropriate retention at the tumor site. CuS NPs that is modified with peptides are prepared facilely, and can aggregate in situ through the intermolecular crosslinking reaction catalyzed by the transglutaminase (TGase) abundantly expressed at the tumor site, resulting in an outstanding photothermal effect for tumor therapy. Upon NIR irradiation, the photothermal effect of CuS‐K and CuS‐Q induced the disintegration of liposomes and prompted the release of CuS‐K, CuS‐Q, and indocyanine green (ICG). Simultaneously, CuS‐K and CuS‐Q aggregated under the catalysis of TGase after being internalized by tumor cells to enhance photothermal therapy. The current study provides valuable inspiration to design nanomedicines with prolonged circulation time in the blood system, better penetration, and retention at the tumor site, and multimodal tumor therapy to achieve the desired therapeutic efficacy.