{"title":"Enhancing cancer immunotherapy with mannose mimicking glycopolymer nanoparticles induced activation of Dendritic cells","authors":"","doi":"10.1016/j.bioorg.2024.107711","DOIUrl":null,"url":null,"abstract":"<div><p>Cancer immunotherapy leverages the immune system’s inherent capacity to combat malignancies. However, effective stimulation of Dendritic cells (DCs) is challenging due to their limited distribution and the immune-suppressive tumor microenvironment. Thus, targeting mannose receptors, which are highly expressed on DCs, represents a promising strategy. This study investigates the development of mannose-based glycopolymer nanoparticles to induce activation of DCs through enhanced antigen presentation. A novel ABA-type triblock bioconjugated glycopolymer (PMn-<em>b</em>-PCL-<em>b</em>-PMn), which mimics mannose was synthesized. This polymer was further modified with Dihexadecyldimethylammonium bromide (DHDAB) to prepare cationic nanoparticles (CMNP) for gene delivery of pCMV-TRP2, an antigenic marker for both melanoma and glioblastoma. The immune response generated by CMNP and the CMNP-TRP2 polyplex was compared to an untreated control following subcutaneous injection in mice. Post-injection cytometric analysis revealed robust DC activation and increased <em>T</em>-cell populations in secondary lymphoid organs, including the spleen and lymph nodes. These findings suggest that CMNP can serve as a potent biomimicking vaccination vehicle against cancer, enhancing the immune response through targeted DCs activation.</p></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0045206824006163","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Cancer immunotherapy leverages the immune system’s inherent capacity to combat malignancies. However, effective stimulation of Dendritic cells (DCs) is challenging due to their limited distribution and the immune-suppressive tumor microenvironment. Thus, targeting mannose receptors, which are highly expressed on DCs, represents a promising strategy. This study investigates the development of mannose-based glycopolymer nanoparticles to induce activation of DCs through enhanced antigen presentation. A novel ABA-type triblock bioconjugated glycopolymer (PMn-b-PCL-b-PMn), which mimics mannose was synthesized. This polymer was further modified with Dihexadecyldimethylammonium bromide (DHDAB) to prepare cationic nanoparticles (CMNP) for gene delivery of pCMV-TRP2, an antigenic marker for both melanoma and glioblastoma. The immune response generated by CMNP and the CMNP-TRP2 polyplex was compared to an untreated control following subcutaneous injection in mice. Post-injection cytometric analysis revealed robust DC activation and increased T-cell populations in secondary lymphoid organs, including the spleen and lymph nodes. These findings suggest that CMNP can serve as a potent biomimicking vaccination vehicle against cancer, enhancing the immune response through targeted DCs activation.
期刊介绍:
Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry.
For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature.
The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.