Puncture-Needle-Integrated Optical Fibers and NIR-II-Activated Thermosensitive Hydrogels for Deep-Seated Tumor Therapy.

Abstract

Deep-seated tumors are difficult to treat because of their location, conventional treatment resistance, and limited light penetration during photothermal therapy (PTT). Interstitial PTT with "inside-out" laser irradiation using optical fibers (OFs) offers a promising solution. This study proposes a drug-device integrated platform assisted by a puncture needle combining stimuli-responsive hydrogels with a spherical-tip polymer OF (SPOF) to overcome dual challenges: Inadequate photothermal agent retention and insufficient optical penetration. The injectable thermosensitive hydrogel (SW8@Gel), composed of Pluronic F127 and aza-boron-dipyrromethene-derived SW8 nanoparticles, rapidly undergoes sol-gel transition at 38°C, facilitating localized and sustained delivery of the photothermal agent. The flexible low-bending-loss SPOF emits 360° divergent near-infrared II (1064 nm) light from its spherical tip, allowing single-fiber illumination of deep-seated tumors (penetration >10 cm) in complex biological environments. Integrating these components enables depth-adaptive tumor ablation. Compared to other methods, the SPOF/SW8@Gel combination demonstrates the lowest frequency and shortest duration for PTT of deep-seated tumors and achieves superior efficacy, with a 90% tumor regression rate in mice models and no off-target damage due to enhanced heating uniformity and reduced systemic toxicity. This platform offers a transformative clinically viable solution for precise ablation of deep malignancies, bridging advanced photonics and targeted oncotherapy.