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Research Article

Arginine-peptide complex-based assemblies to combat tumor hypoxia for enhanced photodynamic therapeutic effect

Yanxian Hou§, Yafei Kuang§, Qikun Jiang, Shuang Zhou, Jiang Yu, Zhonggui He, Jin Sun( )
Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, China

§ Yanxian Hou and Yafei Kuang contributed equally to this work.

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Graphical Abstract

The THPP/Fomc-L3-Arg NPs could rapidly release photosensitizers in tumor cells. Meanwhile, the co-loaded Fmoc-L3-Arg could efficiently generate nitric oxide, inhibiting mitochondrial cellularrespiration and increasing oxygen in tumor cells to support the profound improvement of reactiveoxygen species yield and PDT efficacy. After intravenous injection, the THPP/Fomc-L3-Arg NPsgreatly accumulated at tumor tissue, and significantly inhibited tumor growth upon irradiation. Inconclusion, such an arginine-peptide complex-based nanoassembly addresses the inevitable problemof hypoxia-induced tumor resistance to PDT.

Abstract

Tumor hypoxia is one of the major factors restricting the photodynamic therapy (PDT) efficacy. To address this problem, we designed an arginine-peptide complex, namely Fluorenylmethoxycarbonyl-Leucine-Leucine-Leucine-Arginine-OH (Fmoc-L3-Arg), which is able to co-assemble with 5,10,15,20-Tetrakis (4-hydroxyphenyl) porphyrin (THPP) into stable nanoparticles (NPs) with uniform and spherical shapes. The THPP/Fomc-L3-Arg NPs were ultra-sensitive to tumorous acidic and oxidative conditions, and could rapidly release photosensitizers in tumor cells. Meanwhile, the co-loaded Fmoc-L3-Arg could efficiently generate nitric oxide (NO), inhibiting mitochondrial cellular respiration and increasing oxygen in tumor cells to support the profound improvement of reactive oxygen species (ROS) yield and PDT efficacy. After intravenous injection, the THPP/Fomc-L3-Arg NPs greatly accumulated at tumor tissue and significantly inhibited tumor growth upon irradiation. In conclusion, such an arginine-peptide complex-based nanoassembly addresses the inevitable problem of hypoxia-induced tumor resistance to PDT.

Keywords

arginineco-assemblynitric oxidetumor hypoxiaphotodynamic efficacy

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Nano Research
Volume 15 Issue 6,
June 2022
Pages 5183-5192
DOI: 10.1007/s12274-022-4086-z
Cite this article:
Hou Y, Kuang Y, Jiang Q, et al. Arginine-peptide complex-based assemblies to combat tumor hypoxia for enhanced photodynamic therapeutic effect. Nano Research, 2022, 15(6): 5183-5192. https://doi.org/10.1007/s12274-022-4086-z
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Nano biology

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Received: 23 October 2021
Revised: 14 December 2021
Accepted: 19 December 2021
Published: 06 March 2022
© Tsinghua University Press 2022
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