Cationization to boost both type I and type II ROS generation for photodynamic therapy

Yuewen Yu; Shuang Wu; Le Zhang; Shidang Xu; Chunhui Dai; Shengming Gan; Ganfeng Xie; Guangxue Feng; Ben Zhong Tang

doi:10.1016/j.biomaterials.2021.121255

Cationization to boost both type I and type II ROS generation for photodynamic therapy

Biomaterials. 2022 Jan:280:121255. doi: 10.1016/j.biomaterials.2021.121255. Epub 2021 Nov 17.

Authors

Yuewen Yu¹, Shuang Wu², Le Zhang¹, Shidang Xu³, Chunhui Dai⁴, Shengming Gan¹, Ganfeng Xie⁵, Guangxue Feng⁶, Ben Zhong Tang⁷

Affiliations

¹ AIE Institute, State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510640, China.
² Department of Oncology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
³ Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore, 117585, Singapore.
⁴ Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation, East China University of Technology, Nanchang, 330013, China.
⁵ Department of Oncology, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China. Electronic address: xiegf@aliyun.com.
⁶ AIE Institute, State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510640, China. Electronic address: fenggx@scut.edu.cn.
⁷ AIE Institute, State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, School of Materials Science and Engineering, South China University of Technology, Guangzhou, 510640, China; Shenzhen Institute of Aggregate Science and Technology, School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, 2001 Longxiang Boulevard, Longgang District, Shenzhen City, Guangdong, 518172, China.

PMID: 34810034
DOI: 10.1016/j.biomaterials.2021.121255

Abstract

The pursuing of photosensitizers (PSs) with efficient reactive oxygen species (ROS) especially type I ROS generation in aggregate is always in high demand for photodynamic therapy (PDT) and photoimmunotherapy but remains to be a big challenge. Herein, we report a cationization molecular engineering strategy to boost both singlet oxygen and radical generation for PDT. Cationization could convert the neutral donor-acceptor (D-A) typed molecules with the dicyanoisophorone-triphenylamine core (DTPAN, DTPAPy) to their A-D-A' typed cationic counterparts (DTPANPF₆ and DTPAPyPF₆). Our experiment and simulation results reveal that such cationization could enhance the aggregation-induced emission (AIE) feature, promote the intersystem crossing (ISC) processes, and increase the charge transfer and separation ability, all of which work collaboratively to promote the efficient generation of ROS especially hydroxyl and superoxide radicals in aggregates. Moreover, these cationic AIE PSs also possess specific cancer cell mitochondrial targeting capability, which could further promote the PDT efficacy both in vitro and in vivo. Therefore, we expect this delicate molecular design represents an attractive paradigm to guide the design of type I AIE PSs for the further development of PDT.

Keywords: Aggregation-induced emission; Cationization; Photodynamic therapy; Type I photosensitizers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Neoplasms* / drug therapy
Photochemotherapy* / methods
Photosensitizing Agents / therapeutic use
Reactive Oxygen Species / metabolism
Singlet Oxygen / metabolism

Substances

Photosensitizing Agents
Reactive Oxygen Species
Singlet Oxygen