Gemcitabine nanoparticles promote antitumor immunity against melanoma
Open accessAbstract
Myeloid-derived suppressor cells (MDSCs) promote tumor-mediated immunosuppression and cancer progression. Gemcitabine (Gem) is a MDSC-depleting chemotherapeutic agent; however, its clinical use is hampered by its drug resistance and inefficient in vivo delivery. Here we describe a strategy to formulate a Gem analogue gemcitabine monophosphate (GMP) into a lipid-coated calcium phosphate (LCP) nanoparticle, and investigate its antitumor immunity and therapeutic effects after systemic administrations. In the syngeneic mouse model of B16F10 melanoma, compared with free Gem, the LCP-formulated GMP (LCP-GMP) significantly induced apoptosis and reduced immunosuppression in the tumor microenvironment (TME). LCP-GMP effectively depleted MDSCs and regulatory T cells, and skewed macrophage polarization towards the antitumor M1 phenotype in the TME, leading to enhanced CD8+ T-cell immune response and profound tumor growth inhibition. Thus, engineering the in vivo delivery of MDSC-depleting agents using nanotechnology could substantially modulate immunosuppressive TME and boost T-cell immune response for enhanced antitumor efficacy.
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5-fluorouracil, doxorubicin, gemcitabine, and docetaxel reduced circulating myeloid-derived suppressor cells (MDSCs) in mouse models.
“although 5-fluorouracil, doxorubicin, gemcitabine, and docetaxel reduced circulating myeloid-derived suppressor cells (MDSCs) in mouse models [42–45]”
From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [44]
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References 61 · Cited by 117
Research works printed but not linked: 1
- [22]Li B, Lyophilization of cationic lipid-protamine-DNA (LPD) complexes. J Pharm Sci 89, 355– 364 (2000). 10707016
- Authors
- Zhang, Y., Bush, X., Yan, B., & Chen, J. A.
- Affiliations
- University of Rhode Island (US)
- University of Cincinnati (US)
- Corresponding author
- Zhang, Yuan
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 189
- Pages
- 48-59
- ISSN
- 0142-9612 (ISSN-L)
- PMC
- PMC6281175
- OpenAlex
- W2896879364
- Cited by
- 117
- References
- 61
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 11 · 2023: 13 · 2022: 20 · 2021: 20 · 2020: 18 · 2019: 11
- FWCI
- 5.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (U54GM115677)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- myeloid-derived suppressor cells, melanoma, antitumor immunity, immunosuppressive tumor microenvironment, regulatory T cells, macrophage polarization, CD8+ T cell responses, drug delivery, B16F10 melanoma, nanoparticle formulation
- MeSH terms
- Gemcitabine, Animals, Antineoplastic Agents, Calcium Phosphates, Deoxycytidine, Drug Carriers, Female, Immune Tolerance, Melanoma, Experimental, Mice, Inbred C57BL, CD8-Positive T-Lymphocytes, Cell Line, Tumor, Mice, Nanoparticles, Tumor Microenvironment
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