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.
Zhang et al. (Wed,) studied this question.