{"title":"Biomimetic Self-Oxygenated Immunoliposome for Cancer-Targeted Photodynamic Immunotherapy.","authors":"Yucheng Tang, Tiantian Tang, Yongjiang Li, Junyong Wu, Xinyi Liu, Daxiong Xiang, Xiongbin Hu","doi":"10.2147/IJN.S508696","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Photodynamic therapy (PDT) is a promising strategy with significant clinical application potential for tumor treatment. However, the tumor hypoxia and limited efficacy against tumor metastasis present significant limitations in the clinical application of PDT. To alleviate tumor hypoxia for PDT against tumor growth and metastasis, we developed a self-oxygenated immunoliposome by encapsulating the catalase (CAT) within the liposome cavity and loading the photosensitizer chlorin e6 (Ce6) and immunoadjuvant MPLA in the lipid bilayer of the immunoliposome (CAT@LP-Ce6-A). Subsequently, we fused it with the cancer cell membrane (CCM) to create the hybrid immunoliposome (CAT@LP-CCM-Ce6-A). The in vitro and in vivo anti-cancer efficacy of CAT@LP-CCM-Ce6-A-based photodynamic immunotherapy (PDIT) was evaluated.</p><p><strong>Methods: </strong>CAT@LP-CCM-Ce6-A were characterized by size, zeta potential, transmission electron microscopy (TEM), Coomassie bright blue staining, UV spectrophotometer, and standard Goth's method. Cellular uptake, cell viability, reactive oxygen species (<sup>1</sup>O<sub>2</sub>) generation, calreticulin exposure, and ability to promote BMDCs maturation of CAT@LP-CCM-Ce6-A were evaluated in vitro. Biodistribution, anti-cancer therapeutic efficacy, and in vivo safety of CAT@LP-CCM-Ce6-A were investigated in orthotopic triple-negative breast cancer (TNBC) lung metastasis mouse models.</p><p><strong>Results: </strong>CAT@LP-CCM-Ce6-A was successfully developed via the thin film hydration and co-extrusion method. The loading capacity of Ce6 and CAT was 4.7 ± 0.9% and 8.5 ± 0.9% respectively. CAT@LP-CCM-Ce6-A exhibited improved cellular uptake efficiency and cytotoxicity under laser irradiation against TNBC. Furthermore, CAT@LP-CCM-Ce6-A possessed enhanced anti-enzymatic degradation ability and promotion of DC maturation. In TNBC-bearing mice, CAT@LP-CCM-Ce6-A-based PDIT demonstrated remarkable therapeutic effect and antitumor immunity while maintaining minimal systemic toxicity.</p><p><strong>Conclusion: </strong>CAT@LP-CCM-Ce6-A could be employed as an innovative approach for self-oxygenated photodynamic immunotherapy against cancer.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"20 ","pages":"2743-2759"},"PeriodicalIF":6.6000,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892501/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Nanomedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/IJN.S508696","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"NANOSCIENCE & NANOTECHNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: Photodynamic therapy (PDT) is a promising strategy with significant clinical application potential for tumor treatment. However, the tumor hypoxia and limited efficacy against tumor metastasis present significant limitations in the clinical application of PDT. To alleviate tumor hypoxia for PDT against tumor growth and metastasis, we developed a self-oxygenated immunoliposome by encapsulating the catalase (CAT) within the liposome cavity and loading the photosensitizer chlorin e6 (Ce6) and immunoadjuvant MPLA in the lipid bilayer of the immunoliposome (CAT@LP-Ce6-A). Subsequently, we fused it with the cancer cell membrane (CCM) to create the hybrid immunoliposome (CAT@LP-CCM-Ce6-A). The in vitro and in vivo anti-cancer efficacy of CAT@LP-CCM-Ce6-A-based photodynamic immunotherapy (PDIT) was evaluated.
Methods: CAT@LP-CCM-Ce6-A were characterized by size, zeta potential, transmission electron microscopy (TEM), Coomassie bright blue staining, UV spectrophotometer, and standard Goth's method. Cellular uptake, cell viability, reactive oxygen species (1O2) generation, calreticulin exposure, and ability to promote BMDCs maturation of CAT@LP-CCM-Ce6-A were evaluated in vitro. Biodistribution, anti-cancer therapeutic efficacy, and in vivo safety of CAT@LP-CCM-Ce6-A were investigated in orthotopic triple-negative breast cancer (TNBC) lung metastasis mouse models.
Results: CAT@LP-CCM-Ce6-A was successfully developed via the thin film hydration and co-extrusion method. The loading capacity of Ce6 and CAT was 4.7 ± 0.9% and 8.5 ± 0.9% respectively. CAT@LP-CCM-Ce6-A exhibited improved cellular uptake efficiency and cytotoxicity under laser irradiation against TNBC. Furthermore, CAT@LP-CCM-Ce6-A possessed enhanced anti-enzymatic degradation ability and promotion of DC maturation. In TNBC-bearing mice, CAT@LP-CCM-Ce6-A-based PDIT demonstrated remarkable therapeutic effect and antitumor immunity while maintaining minimal systemic toxicity.
Conclusion: CAT@LP-CCM-Ce6-A could be employed as an innovative approach for self-oxygenated photodynamic immunotherapy against cancer.
期刊介绍：
The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area.
With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field.
Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.
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