Puncture‐Needle‐Integrated Optical Fibers and NIR‐II‐Activated Thermosensitive Hydrogels for Deep‐Seated Tumor Therapy
📄 英文摘要 English 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.
📄 中文摘要 Chinese Abstract
📋 英文结构化总结 English Structured Summary
摘要整理
Background:
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.
Methods:
The platform combined an injectable thermosensitive hydrogel (SW8@Gel), composed of Pluronic F127 and aza-boron-dipyrromethene-derived SW8 nanoparticles, with a flexible low-bending-loss SPOF. SW8@Gel rapidly undergoes sol-gel transition at 38°C, facilitating localized and sustained delivery of the photothermal agent. The 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, and integrating these components enables depth-adaptive tumor ablation.
Results:
The SPOF/SW8@Gel combination demonstrated the lowest frequency and shortest duration for PTT of deep-seated tumors compared to other methods. It achieved 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.
Data Summary:
Quantitative details include a sol-gel transition at 38°C, 360° divergent near-infrared II emission at 1064 nm, tumor penetration >10 cm, and a 90% tumor regression rate in mice models. The combination also showed the lowest frequency and shortest duration for PTT of deep-seated tumors, with no off-target damage.
Conclusions:
The drug-device integrated platform overcomes inadequate photothermal agent retention and insufficient optical penetration, enabling depth-adaptive tumor ablation. It offers a transformative clinically viable solution for precise ablation of deep malignancies, bridging advanced photonics and targeted oncotherapy.
Practical Significance:
This platform provides a clinically viable approach for precise ablation of deep malignancies using interstitial PTT with "inside-out" laser irradiation, addressing the treatment difficulty of deep-seated tumors through localized, sustained photothermal agent delivery and deep optical penetration.
📋 中文结构化总结 Chinese Structured Summary
背景:
深部肿瘤因其位置深、对常规治疗耐药以及光热治疗（PTT）中光穿透受限而难以治疗。采用光纤（OFs）进行“由内向外”激光照射的间质PTT提供了一种有前景的解决方案。本研究提出一种穿刺针辅助的药物-器械一体化平台，将刺激响应水凝胶与球形尖端聚合物光纤（SPOF）相结合，以克服两大挑战：光热剂滞留不足和光学穿透不足。
方法:
该平台将可注射热敏水凝胶（SW8@Gel）与柔性低弯曲损耗SPOF相结合。SW8@Gel由普朗尼克F127（Pluronic F127）和氮杂硼二吡咯甲烷衍生的SW8纳米颗粒组成。SW8@Gel在38°C下可快速发生溶胶-凝胶转变，从而促进光热剂的局部持续递送。SPOF从其球形尖端发射360°发散近红外II区（1064 nm）光，可在复杂生物环境中实现单光纤对深部肿瘤（穿透深度>10 cm）的照射；这些组件的整合可实现深度自适应肿瘤消融。
结果:
与其他方法相比，SPOF/SW8@Gel组合在深部肿瘤PTT中表现出最低的频率和最短的持续时间。由于加热均匀性增强且全身毒性降低，该组合取得了更优疗效，在小鼠模型中肿瘤消退率达90%，且无脱靶损伤。
数据摘要:
定量细节包括38°C下的溶胶-凝胶转变、1064 nm处360°发散近红外II区发射、肿瘤穿透深度>10 cm，以及小鼠模型中90%的肿瘤消退率。该组合还表现出深部肿瘤PTT的最低频率和最短持续时间，且无脱靶损伤。
结论:
该药物-器械一体化平台克服了光热剂滞留不足和光学穿透不足的问题，实现了深度自适应肿瘤消融。它为深部恶性肿瘤的精确消融提供了一种具有变革性且临床可行的解决方案，连接了先进光子学与靶向肿瘤治疗。
实践意义:
该平台利用“由内向外”激光照射的间质PTT，为深部恶性肿瘤的精确消融提供了一种临床可行方法，通过光热剂的局部持续递送和深层光学穿透，解决了深部肿瘤的治疗难题。