Targeted treatment of atherosclerosis with protein–polysaccharide nanoemulsion co-loaded with photosensitiser and upconversion nanoparticles

Abstract

Macrophages are the most abundant cell group in atherosclerosis (AS) lesions and play a vital role in all stages of AS progression. Recent research has shown that reactive oxygen species (ROS) generation from photodynamic therapy (PDT) induces macrophage autophagy to improve abnormal lipid metabolism and inflammatory environment. Especially in macrophage-derived foam cells, which has become a potential strategy for the treatment of AS. In this study, we prepared the conjugate (DB) of dextran (DEX) and bovine serum albumin (BSA). The DB was used as the emulsifier to prepare nanoemulsion loaded with upconversion nanoparticles (UCNPs) and chlorin e6 (Ce6) (UCNPs-Ce6@DB). The DEX modified on the surface of the nanoemulsion can recognise and bind to the scavenger receptor class A (SR-A) highly expressed on macrophages and promote the uptake of macrophage-derived foam cells in AS plates through SR-A-mediated endocytosis. In addition, UCNPs-Ce6@DB-mediated PDT enhanced ROS generation and induced autophagy in macrophage-derived foam cells, enhanced the expression of ABCA1, a protein closely related to cholesterol efflux, and inhibited the secretion of pro-inflammatory cytokines. Ultimately, UCNPs-Ce6@DB was shown to inhibit plaque formation in mouse models of AS. In conclusion, UCNPs-Ce6@DB offers a promising treatment for AS.

Keywords:

• Photodynamic therapy
• chlorin e6
• upconversion nanoparticles
• protein-polysaccharide
• nanoemulsion
• autophagy
• atherosclerosis

Authors’ contributions

Jing Huang: investigation, formal analysis, data curation, writing, and editing. Shan Xu: visualisation, investigation, validation, and writing. Lina Liu: investigation, writing, review, and editing. Jiyuan Zhang: investigation and validation. Jinzhuan Xu: investigation. Lili Zhang: investigation. Xiang Zhou: investigation. Lei Huang: investigation. Jianqing Peng: review and editing. Jianing Wang: methodology, conceptualisation, supervision, funding acquisition. Zipeng Gong: supervision, project administration, funding acquisition. Yi Chen: conceptualisation, methodology, supervision, funding acquisition.

Disclosure statement

The authors declare no competing financial interest.

Data availability statement

All data are included in the manuscript and supplemental material.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [81960333], the Natural Science Research Foundation of Guizhou Provincial Department of Education (qianjiaoji[2023]066), the Excellent Young Talents Plan of Guizhou Province (QKHPTRC-YQK[2023]029, QKHPTRC(2021)-5632), The Natural Science Research Project of Higher Education Institutions in Jiangsu Province (23KJB310008), Doctor of Entrepreneurship and Innovation Funds of Jiangsu (JSSCBS20222019), The General Project of Nanjing Medical Science and Technology Development Fund (YKK22223), The General Project of Youth Innovation and Scientific Research Fund of the Affiliated Jiangning Hospital with Nanjing Medical University (JNYYZXKY202210), The General Project of Nanjing Medical University Science and Technology Development Fund (NMUB20220155), National college students innovation and entrepreneurship training program (S202210660140).