In-vitro immune-modulation of triple-negative breast cancer through targeting miR-30a-5p/MALAT1 axis using nano-PDT combinational approach
Background: Triple negative breast cancer (TNBC) is an immunogenic tumor; however, its tumor immune microenvironment (TIME) is densely packed with immune suppressive cytokines and immune checkpoints. The immune-suppressive features of TNBC TIME represent a considerable obstacle to any immunotherapeu...
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Elsevier
2025-05-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523325000968 |
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| author | Asmaa Ramzy Mohammad Abdel-Halim Tamer Manie Noha M. Elemam Samar Mansour Rana A. Youness Aya Sebak |
| author_facet | Asmaa Ramzy Mohammad Abdel-Halim Tamer Manie Noha M. Elemam Samar Mansour Rana A. Youness Aya Sebak |
| author_sort | Asmaa Ramzy |
| collection | DOAJ |
| description | Background: Triple negative breast cancer (TNBC) is an immunogenic tumor; however, its tumor immune microenvironment (TIME) is densely packed with immune suppressive cytokines and immune checkpoints. The immune-suppressive features of TNBC TIME represent a considerable obstacle to any immunotherapeutic approach. The objective of this study was to develop a multimodal in-vitro strategy to manipulate the TNBC TIME and enhance patients' outcomes by employing carefully tailored hybrid chitosan-lipid Nanoparticles (CLNPs), metformin and chlorin e6 (Ce-6)-mediated PDT, alone or combined. Special focus is directed towards evaluation of the role of the selected treatment agents on the non-coding RNAs (ncRNAs) involved in tuning the immuno-oncogenic profile of TNBC, for instance, the miR-30a-5p/MALAT1 network. Methods: This study enrolled 30 BC patients. CLNPs and ce-6-loaded CLNPs with different physicochemical features were synthesized and optimized using ionotropic gelation. The intracellular concentration and effects on MDA-MB-231 cellular viability were investigated. UHPLC was used to quantify ce-6. MDA-MB-231 cells were transfected with miR-30a-5p oligonucleotides and MALAT1 siRNAs using lipofection to investigate the interaction between MIF, PD-L1, TNF-α, IL-10, and the miR-30a-5p/MALAT1 ceRNA network. qRT-PCR was used to evaluate IL-10, TNF-α, and MIF expression levels, whereas flow cytometry was used for PD-L1. Results: Immunophenotyping of BC biopsies revealed significantly elevated levels of immunosuppressive markers, including IL-10, TNF-α, PD-L1, and MIF in BC biopsies compared to its normal counterparts. Upon patient stratification, it was shown that MIF and IL-10 are upregulated in TNBC patients compared to non-TNBC patients. Nonetheless, immune suppressive biomarkers expression investigated in the current study was generally correlated with signs of poor prognosis. CLNPs with mean particle size ranging from 50-150 nm were obtained. CLNPs exhibited different patterns of intracellular uptake, cytotoxicity and modulation of the immunosuppressive markers based on their physicochemical properties and composition. In particular, CLNP4 in-vitro effectively reduced IL-10, TNF-α, MIF, and PD-L1. Loading of Ce-6 into CLNP4 (Ce6-CLNPs) improved the in-vitro cytotoxic effects via PDT. In addition, PDT with Ce6-CLNP4 enhanced the expression of tumor-suppressive miR-30a-5p and decreased oncogenic lncRNA MALAT1 expression in MDA-MB-231 cells, suggesting a potential for modulating the TNBC immuno-oncogenic profile. Conclusion: This study demonstrated that CLNPs and Ce-6-mediated PDT can modulate several key immunosuppressive factors and the miR-30a-5p/MALAT1 axis in TNBC cells. These findings provide a rationale for further in-vivo investigation of this multimodal therapeutic strategy. |
| format | Article |
| id | doaj-art-e647135645b3465ea895600109874297 |
| institution | OA Journals |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
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| series | Translational Oncology |
| spelling | doaj-art-e647135645b3465ea8956001098742972025-08-20T02:09:40ZengElsevierTranslational Oncology1936-52332025-05-015510236510.1016/j.tranon.2025.102365In-vitro immune-modulation of triple-negative breast cancer through targeting miR-30a-5p/MALAT1 axis using nano-PDT combinational approachAsmaa Ramzy0Mohammad Abdel-Halim1Tamer Manie2Noha M. Elemam3Samar Mansour4Rana A. Youness5Aya Sebak6Department of Pharmaceutical Technology, Faculty of Pharmacy & Biotechnology, The German University in Cairo, New Cairo 11835, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy & Biotechnology, The German University in Cairo, New Cairo 11835, EgyptDepartment of Breast Surgery, National Cancer Institute, Cairo University, Cairo, EgyptClinical Sciences Department, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab EmiratesDepartment of Pharmaceutical Technology, Faculty of Pharmacy & Biotechnology, The German University in Cairo, New Cairo 11835, EgyptDepartment of Molecular Biology and Biochemistry, Molecular Genetics Research Team (MGRT), Faculty of Biotechnology, German International University (GIU), New Administrative Capital, Cairo 11835, Egypt; Corresponding authors.Department of Pharmaceutical Technology, Faculty of Pharmacy & Biotechnology, The German University in Cairo, New Cairo 11835, Egypt; Corresponding authors.Background: Triple negative breast cancer (TNBC) is an immunogenic tumor; however, its tumor immune microenvironment (TIME) is densely packed with immune suppressive cytokines and immune checkpoints. The immune-suppressive features of TNBC TIME represent a considerable obstacle to any immunotherapeutic approach. The objective of this study was to develop a multimodal in-vitro strategy to manipulate the TNBC TIME and enhance patients' outcomes by employing carefully tailored hybrid chitosan-lipid Nanoparticles (CLNPs), metformin and chlorin e6 (Ce-6)-mediated PDT, alone or combined. Special focus is directed towards evaluation of the role of the selected treatment agents on the non-coding RNAs (ncRNAs) involved in tuning the immuno-oncogenic profile of TNBC, for instance, the miR-30a-5p/MALAT1 network. Methods: This study enrolled 30 BC patients. CLNPs and ce-6-loaded CLNPs with different physicochemical features were synthesized and optimized using ionotropic gelation. The intracellular concentration and effects on MDA-MB-231 cellular viability were investigated. UHPLC was used to quantify ce-6. MDA-MB-231 cells were transfected with miR-30a-5p oligonucleotides and MALAT1 siRNAs using lipofection to investigate the interaction between MIF, PD-L1, TNF-α, IL-10, and the miR-30a-5p/MALAT1 ceRNA network. qRT-PCR was used to evaluate IL-10, TNF-α, and MIF expression levels, whereas flow cytometry was used for PD-L1. Results: Immunophenotyping of BC biopsies revealed significantly elevated levels of immunosuppressive markers, including IL-10, TNF-α, PD-L1, and MIF in BC biopsies compared to its normal counterparts. Upon patient stratification, it was shown that MIF and IL-10 are upregulated in TNBC patients compared to non-TNBC patients. Nonetheless, immune suppressive biomarkers expression investigated in the current study was generally correlated with signs of poor prognosis. CLNPs with mean particle size ranging from 50-150 nm were obtained. CLNPs exhibited different patterns of intracellular uptake, cytotoxicity and modulation of the immunosuppressive markers based on their physicochemical properties and composition. In particular, CLNP4 in-vitro effectively reduced IL-10, TNF-α, MIF, and PD-L1. Loading of Ce-6 into CLNP4 (Ce6-CLNPs) improved the in-vitro cytotoxic effects via PDT. In addition, PDT with Ce6-CLNP4 enhanced the expression of tumor-suppressive miR-30a-5p and decreased oncogenic lncRNA MALAT1 expression in MDA-MB-231 cells, suggesting a potential for modulating the TNBC immuno-oncogenic profile. Conclusion: This study demonstrated that CLNPs and Ce-6-mediated PDT can modulate several key immunosuppressive factors and the miR-30a-5p/MALAT1 axis in TNBC cells. These findings provide a rationale for further in-vivo investigation of this multimodal therapeutic strategy.http://www.sciencedirect.com/science/article/pii/S1936523325000968Tumor microenvironmentPDTTNBCNanomaterialsMALAT1Immunotherapy |
| spellingShingle | Asmaa Ramzy Mohammad Abdel-Halim Tamer Manie Noha M. Elemam Samar Mansour Rana A. Youness Aya Sebak In-vitro immune-modulation of triple-negative breast cancer through targeting miR-30a-5p/MALAT1 axis using nano-PDT combinational approach Translational Oncology Tumor microenvironment PDT TNBC Nanomaterials MALAT1 Immunotherapy |
| title | In-vitro immune-modulation of triple-negative breast cancer through targeting miR-30a-5p/MALAT1 axis using nano-PDT combinational approach |
| title_full | In-vitro immune-modulation of triple-negative breast cancer through targeting miR-30a-5p/MALAT1 axis using nano-PDT combinational approach |
| title_fullStr | In-vitro immune-modulation of triple-negative breast cancer through targeting miR-30a-5p/MALAT1 axis using nano-PDT combinational approach |
| title_full_unstemmed | In-vitro immune-modulation of triple-negative breast cancer through targeting miR-30a-5p/MALAT1 axis using nano-PDT combinational approach |
| title_short | In-vitro immune-modulation of triple-negative breast cancer through targeting miR-30a-5p/MALAT1 axis using nano-PDT combinational approach |
| title_sort | in vitro immune modulation of triple negative breast cancer through targeting mir 30a 5p malat1 axis using nano pdt combinational approach |
| topic | Tumor microenvironment PDT TNBC Nanomaterials MALAT1 Immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S1936523325000968 |
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