An Acceptor-Donor-Acceptor Structured Small Molecule for Effective NIR Triggered Dual Phototherapy of Cancer
An Acceptor-Donor-Acceptor Structured Small Molecule for Effective NIR Triggered Dual Phototherapy of Cancer
复制标题
用于有效近红外触发癌症双重光疗的受体-供体-受体结构小分子
DOI：
10.1002/adfm.201910301
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发表时间：
2020-02-24
影响因子：
19
通讯作者：
Chen, Yongsheng
中科院分区：
文献类型：
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作者：
He, Zheng;Zhao, Linlin;Chen, Yongsheng
双重光疗，包括光动力疗法（PDT）和光热疗法（PTT），被认为是一种比单一PDT或PTT更有效的癌症治疗方法。然而，开发用于有效双重光疗的单组分和近红外（NIR）触发剂仍然是一个挑战。本文提出了一种开发用于PDT和PTT联合治疗的双功能小分子光敏剂的简单策略：1）精细地调节HOMO-LUMO能级以调节用于PDT的有效单线态氧（O-1（2））产生的系统间交叉（ISC）过程; 2）通过强的分子内电荷转移（ICT）有效抑制荧光，以最大化用于PTT或用于PDT的ISC过程的光能到热的转化。设计并合成了一种受体-供体-受体（A-D-A）结构的小分子（CPDT）。通过直接用叶酸官能化的两亲性共聚物包封CPDT制备的生物相容性纳米颗粒FA-CNPs在单次808 nm激光照射下表现出强的NIR吸收、稳健的光稳定性、癌细胞靶向、高光热转换效率以及高效的O-1（2）产生。此外，FA-CNP在体内的协同PDT和PTT效应通过显著抑制肿瘤生长来证明。该策略为合理设计和开发安全有效的光敏剂提供了新的途径。
Dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is regarded as a more effective method for cancer treatment than single PDT or PTT. However, development of single component and near-infrared (NIR) triggered agents for efficient dual phototherapy remains a challenge. Herein, a simple strategy to develop dual-functional small-molecules-based photosensitizers for combined PDT and PTT treatment is proposed through: 1) finely modulating HOMO-LUMO energy levels to regulate the intersystem crossing (ISC) process for effective singlet oxygen (O-1(2)) generation for PDT; 2) effectively inhibiting fluorescence via strong intramolecular charge transfer (ICT) to maximize the conversion of photo energy to heat for PTT or ISC process for PDT. An acceptor-donor-acceptor (A-D-A) structured small molecule (CPDT) is designed and synthesized. The biocompatible nanoparticles, FA-CNPs, prepared by encapsulating CPDT directly with a folate functionalized amphipathic copolymer, present strong NIR absorption, robust photostability, cancer cell targeting, high photothermal conversion efficiency as well as efficient O-1(2) generation under single 808 nm laser irradiation. Furthermore, synergistic PDT and PTT effects of FA-CNPs in vivo are demonstrated by significant inhibition of tumor growth. The proposed strategy may provide a new approach to reasonably design and develop safe and efficient photosensitizers for dual phototherapy against cancer.