Grade-Targeted Nanoparticles for Improved Hypoxic Tumor Microenvironment and Enhanced Photodynamic Cancer Therapy

Abstract

Background: The hypoxia of the tumor microenvironment (TME), low transfer efficiency of photosensitizers and limited diffusion distance of reactive oxygen species restrict the application of photodynamic therapy (PDT). Aim: To produce TME-responsive and effective nanoparticles for sensitizing PDT. Materials & methods: CD44 and mitochondria grade-targeted hyaluronic acid (HA)-triphenylphosphine (TPP)-aminolevulinic acid (ALA)-catalase (CAT) nanoparticles (HTACNPs) were synthesized via a modified double-emulsion method. In vitro and in vivo experiments were performed to investigate the antitumor efficacy of HTACNP-mediated PDT. Results: HTACNPs specifically targeted MV3 cells and the mitochondria and produced O₂ to relieve TME hypoxia. HTACNP-mediated PDT produced reactive oxygen species to induce irreversible cell apoptosis. HTACNP-PDT inhibited melanoma growth effectively in vivo. Conclusion: HTACNP-mediated PDT improved TME hypoxia and effectively enhanced PDT for cancer.

Keywords::

• grade targeted
• hypoxic tumor microenvironment
• melanoma
• nanoparticle
• photodynamic therapy

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/nnm-2020-0096

Author contributions

The manuscript was written through the contributions of all the authors. All authors have given approval to the final version of the manuscript. Y-K Tao, X-Y Hou and G Jiang designed the experimental approaches and wrote the manuscript. Y-K Tao and X-X Li performed the experiments, and Y-K Tao and F-M Zuo analyzed data and took on the statistical analysis.

Financial & competing interests disclosure

This research was supported by the National Natural Science Foundation of China (Nos. 81872493, 81803151), the China Postdoctoral Science Foundation (Nos. 2016M590505, 2017T100407), the Jiangsu Provincial Medical Talent 500 Foundation, the ‘Six Talent Peaks’ Project of Jiangsu Province (Nos. WSW-074, WSN-254) and the Innovation of Graduate Student Training Projects in Jiangsu Province of China (No. KYCX19_2230). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was provided by EnPapers Company.

Data sharing statement

The data used to support the findings of this study are available from the corresponding author upon request.

Ethical conduct of research

All the animals used in the experiments received care in compliance with the Guide for the Care and Use of Laboratory Animals and the Principles of Laboratory Animal Care. All the animal experiments were performed in accordance with the principles and procedures approved by the Committee on the Ethics of Animal Experiments of Xuzhou Medical University.

Acknowledgments

5-ALA (aminolevulinic acid hydrochloride) and LD600-C semiconductor laser therapy apparatus was supported by Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd. The authors are grateful to Fudan-Zhangjiang company’s product and technical support.

Additional information

Funding

This research was supported by the National Natural Science Foundation of China (Nos. 81872493, 81803151), the China Postdoctoral Science Foundation (Nos. 2016M590505, 2017T100407), the Jiangsu Provincial Medical Talent 500 Foundation, the ‘Six Talent Peaks’ Project of Jiangsu Province (Nos. WSW-074, WSN-254) and the Innovation of Graduate Student Training Projects in Jiangsu Province of China (No. KYCX19_2230). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.