MBene as a Theranostic Nanoplatform for Photocontrolled Intratumoral Retention and Drug Release

Tumor-targeted drug delivery by nanomaterials is important to improve tumor therapy efficacy and reduce toxic side effects, but its efficiency is quite limited. In this work, a new type of MBene, zirconium boride nanosheet (ZBN), as a versatile nanoplatform to realize near-infrared (NIR)-controlled intratumoral retention and drug release is developed. ZBN exhibits high NIR-photothermal conversion efficiency (76.8%), surface modification with hyaluronic acid (HA) by polyol-borate esterfication endows ZBN-HA with good dispersion, and the photopyrolysis of borate ester causes HA detachment and ZBN aggregation, enabling NIR-controlled intratumoral retention to achieve high intratumoral accumulation. By virtue of surface borate esterfication, polyol chemotherapeutic drug (doxorubicin, DOX), and NO prodrug (β-galactosyl-diazeniumdiolate, Gal-NO) can be efficiently and stably conjugated on the surface of ZBN-HA (1.21 g DOX or 0.57 g Gal-NO per gram ZBN) without visible drug leakage, and the photopyrolysis of borate ester enables NIR-controlled drug release with high responsiveness and controllability. Combined chemothermal/gasothermal therapies based on ZBN-HA/DOX and ZBN-HA/NO nanomedicines eradicate primary tumors and interdict tumor metastasis by changing the tumor microenvironment and killing cancer cells in primary tumors. The developed NIR-photothermal MBene is confirmed as a versatile nanoplatform capable of high-efficacy tumor-targeted drug delivery and controlled drug release.