A Dual-Layer MOF Microneedle Patch for Self-Sensitized Mild Photothermal Therapy and Autophagy Regulation.

The integration of autophagy regulation with photothermal therapy (PTT) presents a promising therapeutic strategy for addressing triple-negative breast cancer (TNBC), a condition where current treatment modalities are hindered by limited tissue penetration and therapeutic resistance. In this study, we have developed a dual-layer metal-organic framework (MOF) integrated microneedle patch (DMMN) designed to facilitate sequential dissolution for combination therapy, encompassing sensitized PTT, autophagy regulation, and chemotherapy. The outer layer of the microneedle is constructed from a hyaluronic acid (HA) matrix, which is integrated with carboxyl MOFs loaded with Apoptozole (Az), an Hsp70 inhibitor. This configuration maintains rapid dissolution behavior and exhibits favorable mechanical properties. The core layer consists of hyaluronic acid methacryloyl (HAMA), which encapsulates photothermal agents and degrades slowly to enable deep-tissue penetration for effective PTT. The incorporated MOFs enhance the mechanical strength of the HA-based microneedles and improve the loading efficiency of hydrophobic drugs. Upon tissue penetration, the released Az inhibits Hsp70, thereby sensitizing cancer cells to PTT, promoting lysosome-mediated apoptosis, and suppressing autophagy. This dual-layer MOF-integrated microneedle system offers a novel approach to overcoming the challenges associated with TNBC treatment.