Enhanced Anticancer Effects Through Combined Therapeutic Model of Macrophage Polarization and Cancer Cell Apoptosis by Multifunctional Lipid Nanocomposites
Issued Date
2025-03-01
Resource Type
ISSN
15493296
eISSN
15524965
Scopus ID
2-s2.0-85219141500
Pubmed ID
39972623
Journal Title
Journal of Biomedical Materials Research - Part A
Volume
113
Issue
3
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Biomedical Materials Research - Part A Vol.113 No.3 (2025)
Suggested Citation
Rodponthukwaji K., Khowawisetsut L., Limjunyawong N., Kunwong N., Duangchan K., Sripinitchai S., Sathornsumetee S., Nguyen T., Srisawat C., Punnakitikashem P. Enhanced Anticancer Effects Through Combined Therapeutic Model of Macrophage Polarization and Cancer Cell Apoptosis by Multifunctional Lipid Nanocomposites. Journal of Biomedical Materials Research - Part A Vol.113 No.3 (2025). doi:10.1002/jbm.a.37886 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/105584
Title
Enhanced Anticancer Effects Through Combined Therapeutic Model of Macrophage Polarization and Cancer Cell Apoptosis by Multifunctional Lipid Nanocomposites
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Abstract
Although the mono-anticancer therapy approach particularly directly targeting tumors is still common, this conventional method is generally deemed not effective and insufficient. In tumor microenvironment (TME), tumor-associated macrophages (TAMs, referred to as M2-polarized) play a crucial role in creating an immunosuppressive TME, contributing to various pro-tumorigenic effects. A promising strategy to inhibit tumor growth involves re-educating M2 macrophages into tumoricidal macrophages (M1). Therefore, combining macrophage reprogramming with cancer cell death induction in a single modality may offer synergistic benefits in cancer therapy. Here, we engineered a lipid-based delivery platform capable of co-delivering resiquimod (R848) and polyinosinic: polycytidylic acid (PIC). R848 in our nanosystem effectively triggered M2-to-M1 repolarization, as evidenced by the upregulation of M1 marker genes (TNF, IL6), the release of proinflammatory cytokines (TNF-α and IL-6), and the downregulation of the M2 marker gene, MRC1. On the other hand, the presence of PIC increased caspase-3/7 activity leading to cancer cell death through the apoptotic pathway. This nanocarrier system established a multifunctional platform to enhance the anticancer effect. The synergistic effect of repolarized macrophages in combination with the induction of apoptosis, facilitated by our nanomedicine, was evident in a co-culture system of macrophage and cancer cells, showing a significant increase in cancer cell death compared to individual treatments. These findings attractively demonstrated the potential of our multifunctional lipid nanoparticles as therapeutic agents for anticancer treatment by modulating the tumor immune microenvironment and simultaneously increasing cancer cell cytotoxicity.