Abstract
Hypoxia severely impedes the therapeutic efficacies of tumor chemotherapy, radiotherapy and conventional photodynamic therapy (type II PDT). Herein, we proposed a nonplanar near-infrared (NIR)-absorbing hyperthermia and superoxide radical (O2−•) photogenerator (TB) against hypoxic tumors. TB particularly possessed a favorable O2−• generation capability under 808 nm laser irradiation with the donor-acceptor-donor (D-A-D) molecular structure. Moreover, owing to molecular rotation, potent hyperthermia was realized under continuous laser irradiation. For the usage of hypoxic tumor treatment, TB was encapsulated by a block copolymer, poly(ethylene glycol)-b-poly(latic acid) (PEG45-b-PLA24), to fabricate phototheranostic nanoparticles (TB NPs). Due to the twisted molecular structure and the shielding effect of long alkyl chains, the π-π stacking-induced quenching of O2−• could be reduced after the fabrication of nano-assemblies. Significantly, TB NPs exhibited satisfactory O2−• generation for type I PDT and a simultaneously distinct photothermal conversion efficiency (PCE, 62%) for photothermal therapy (PTT) to combat hypoxic tumor cells. Moreover, the high PCE endowed TB NPs with high performance photoacoustic (PA) and photothermal imaging capability. In vivo experiments demonstrated that TB NPs possessed an outstanding phototherapeutic efficacy for eradicating hypoxic tumors. This study established a novel approach for constructing oxygen-independent phototherapeutic reagent against hypoxic tumors
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摘要
肿瘤乏氧微环境严重抑制了肿瘤化疗、放疗及II型光动力 治疗的疗效. 因此, 开发非氧气依赖性的肿瘤治疗方式具有重要意 义. 在此, 我们设计了一种超稳定的近红外吸收的光热和超氧自由 基(O2−•)供体(TB). 由于D-A-D分子结构, 在808 nm激光照射下, TB 能够产生大量O2−•. 此外, 由于电子供体同时还充当了转子基元, TB还能够在连续激光照射下产生极强的光热. 为了将TB应用于乏 氧肿瘤治疗, TB被嵌段共聚物PEG45-b-PLA24封装以制成纳米颗粒 (TB NPs). 扭曲的分子结构和长烷基链的屏蔽效应有效降低了组 装体由于聚集所导致的O2−•淬灭. 组装而成的TB NPs仍具有令人 满意的O2−•生成能力和较高的光热转化效率, 因而TB NPs可被用 于乏氧肿瘤治疗. 此外, 由于TB NPs的光热转换效率较高, 其可被 用于光声成像和光热成像. 在活体抗肿瘤实验中, 通过连续光照, TB NPs可以完全消除乏氧肿瘤. 本研究为设计非氧依赖性的光疗 试剂用于乏氧肿瘤治疗提供了一种全新的策略.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (21875063 and 21871006), the Science and Technology Commission of Shanghai Municipality for Shanghai International Cooperation Program (19440710600), and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering.
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Zhu Y, Wu Q, Hao E, and Zhang W conceived and designed the project; Zhu Y and Wu Q analyzed the data; Chen C, Yang G contributed to the cell and animal experiments; Zhu Y and Wu Q wrote the paper with the support from Cao H and Gao Y; Jiao L, Hao E and Zhang W provided the technical support. All authors have given approval to the final version of the manuscript.
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Weian Zhang is a full professor in polymer science at the East China University of Science and Technology. He received his PhD degree from the University of Science and Technology of China (USTC) in 2003. Prior to his independent work, he worked at the University of Bayreuth in Germany as a Humboldt fellow and the University of Leeds in UK as a Marie Curie fellow. His research interests concern preparation, self-assembly and application of photosensitive polymers.
Erhong Hao joined Anhui Normal University after he received his PhD degree from Louisiana State University in 2007. He also received a Master’s degree at USTC and a Bachelor’s degree from Shandong University. He has been a full professor at the College of Chemistry and Materials Science since 2009. His research focuses on developing new fluorescent dyes and their applications as smart molecular probes, advanced imaging reagents and photosensitizers.
Lijuan Jiao received her Bachelor’s degree (2000) from Shandong University, China, and her Master’s degree (2003) from USTC. She obtained her PhD degree (2007) from Louisiana State University (USA). She joined Anhui Normal University in 2008, and became a full professor (2010) at the College of Chemistry and Materials Science. Her research focuses on the development of novel BODIPY and porphyrin-related dyes, understanding their photophysical properties and studying their optoelectrical and biological applications. She received an SPP/JPP Young Investigator Award for her research in BODIPY and oligopyrrole chemistry in 2016.
Yucheng Zhu received his BA degree from the East China University of Science and Technology, in 2016. He is a doctoral candidate under the supervision of Prof. Weian Zhang and Prof. Yun Gao at the East China University of Science and Technology. His current research interest focuses on the phototherapy of functional photosensitizers.
Qinghua Wu received his PhD degree under the supervision of Prof. Lijuan Jiao from Anhui Normal University, China, in 2019. He is now a postdoctoral fellow at Anhui Normal University. His current research interests focus on the design and synthesis of fluorescent dyes, their photophysical properties and biological applications.
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The authors declare that they have no conflict of interest.
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A NIR-absorbing superoxide radical and hyperthermia photogenerator via twisted donor-acceptor-donor molecular rotation for hypoxic tumor eradication
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Zhu, Y., Wu, Q., Chen, C. et al. NIR-absorbing superoxide radical and hyperthermia photogenerator via twisted donor-acceptor-donor molecular rotation for hypoxic tumor eradication. Sci. China Mater. 64, 3101–3113 (2021). https://doi.org/10.1007/s40843-021-1706-4
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DOI: https://doi.org/10.1007/s40843-021-1706-4