State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Pokfulam, Hong Kong, China.
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
J Nanobiotechnology. 2021 Nov 4;19(1):357. doi: 10.1186/s12951-021-01103-z.
Photoresponsive drug delivery can achieve spatiotemporal control of drug accumulation at desired sites. Long-wavelength light is preferable owing to its deep tissue penetration and low toxicity. One-photon upconversion-like photolysis via triplet-triplet energy transfer (TTET) between photosensitizer and photoresponsive group enables the use of long-wavelength light to activate short-wavelength light-responsive groups. However, such process requires oxygen-free environment to achieve efficient photolysis due to the oxygen quenching of triplet excited states.
Herein, we report a strategy that uses red light to trigger disassembly of small-molecule nanoparticles by one-photon upconversion-like photolysis for cancer therapy. A photocleavable trigonal molecule, BTAEA, self-assembled into nanoparticles and enclosed photosensitizer, PtTPBP. Such nanoparticles protected TTET-based photolysis from oxygen quenching in normoxia aqueous solutions, resulting in efficient red light-triggered BTAEA cleavage, dissociation of nanoparticles and subsequent cargo release. With paclitaxel as the model drug, the red light-triggered drug release system demonstrated promising anti-tumor efficacy both in vitro and in vivo.
This study provides a practical reference for constructing photoresponsive nanocarriers based on the one-photon upconversion-like photolysis.
光响应药物输送可以实现药物在所需部位的时空控制积累。由于其具有深组织穿透性和低毒性,长波长光更可取。光致剂和光响应基团之间的三重态-三重态能量转移(TTET)的单光子上转换类似光解作用使我们能够使用长波长光来激活短波长光响应基团。然而,由于三重态激发态的氧猝灭,这种过程需要无氧环境才能实现有效的光解。
本文报道了一种使用红光通过单光子上转换类似光解作用触发小分子纳米颗粒解体的策略,用于癌症治疗。一种光可裂解的三角分子 BTAEA 自组装成纳米颗粒并包封光敏剂 PtTPBP。这些纳米颗粒保护基于 TTET 的光解作用免受常氧水相中氧的猝灭,从而实现高效的红光触发 BTAEA 裂解、纳米颗粒解离和随后的货物释放。以紫杉醇为模型药物,该红光触发的药物释放系统在体外和体内均表现出有希望的抗肿瘤功效。
本研究为基于单光子上转换类似光解作用构建光响应纳米载体提供了实用参考。