Molecular Stacking@Infinite Coordination Polymer Nanocomposites for Tumor Continuous High-Intensity Photothermal-Thermodynamic Alternate Cycle Therapy and Chemotherapy.

Abstract

To enhance synergistic therapeutic efficiency of tumor photothermal-thermodynamic-chemotherapy and address challenges of limited laser penetration, uneven heating, and poor temporal coordination among therapeutic modalities, we fabricated a photomicroneedle (PMN) system consisting of an optical fiber integrated into a perforated stainless-steel microneedle, in which the laser delivered via the PMN is emitted both from the tip and the sidewalls, enabling uniform intratumoral irradiation. The PMN-assisted tumor continuous high-intensity photothermal-thermodynamic alternate cycle therapy and chemotherapy strategy that consistently keeps over 90% tumor cell death within 48 h was developed. To implement this strategy, dual-layer nanocomposites were engineered by self-assembling IR825 and doxorubicin (DOX) into core nanoparticles (Dp825 NPs), which were then encapsulated in polydopamine (PDA)-Fe(III)-folic acid (FA) infinite coordination polymer (ICP) shell loaded with artesunate (ARS), forming nanocomposites (Dp825:ARS@PDA-Fe(III)-FA ICP NCPs). The resulting nanocomposites have high drug loading and tumor targeting efficiency, enabling precise spatiotemporal control of drug release to meet the requirements of the above coordinated strategy. In vivo studies demonstrated complete eradication of large tumors (∼300 mm3) without recurrence over 60 days, using only 300 mW·cm-2 laser power and a total injection dose of 5.0 mg·kg-1, which offers a promising platform for highly effective and minimally side-effect tumor therapy.