{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ryu Y"],"funding":["Mid-Career Researcher Program","Intramural Research Program of the Korea Institute of Science and Technology","Ministry of Science and ICT, South Korea","Korea Institute of Science and Technology"],"pagination":["e04468"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12423919"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["21(36)"],"pubmed_abstract":["Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that lacks estrogen receptor, progesterone receptor, and HER2 expression, which limits the efficacy of targeted therapies. MicroRNA-34a-5p (miR-34a), a tumor-suppressor miRNA known for regulating oncogenic pathways, initially appeared promising as a therapeutic avenue. However, the clinical translation of miR-34a has been hindered by challenges such as poor stability, inefficient cytoplasmic delivery, and immune-related toxicities, as evidenced by the failure of MRX34 in trials. To address these limitations, this study developes a novel antibody-oligonucleotide conjugate (AOC) platform anti-CD47-miR-34a conjugate (aCD47-C-miR34a). The aCD47-C-miR34a system combines the anti-CD47 antibodies with miR-34a using a bioreducible linker, ensuring targeted cytoplasmic delivery via CD47-mediated endocytosis and endosomal escape. CD47, an immune checkpoint protein overexpressed in TNBC, facilitates immune evasion, making it an attractive therapeutic target. In preclinical TNBC models, aCD47-C-miR34a successfully restored miR-34a's tumor-suppressive functions by downregulating oncogenic pathways including PD-L1, while modulating the tumor microenvironment. This dual mechanism promoted macrophage phagocytosis, enhanced CD8<sup>+</sup> T-cell activation, and induced apoptosis, resulting in significant tumor inhibition without systemic toxicity. These findings demonstrate the transformative potential of aCD47-C-miR34a in overcoming TNBC's oncogenic and immune-evasive mechanisms, paving the way for innovative treatments in TNBC and other heterogeneous, aggressive cancers."],"journal":["Small (Weinheim an der Bergstrasse, Germany)"],"pubmed_title":["Targeted Delivery of miR-34a via Anti-CD47 Antibody Conjugates for Enhanced Cancer Immunotherapy in Triple Negative Breast Cancer."],"pmcid":["PMC12423919"],"funding_grant_id":["RS‐2024‐00453114","NRF-2022R1A2C2006861","RS-2024-00453114"],"pubmed_authors":["Kim EH","Shim MK","Kim SH","Yang Y","Jang Y","Jang H","Kim Y","Ryu Y","Choi J","Park B","Chi SG","Yoon HY"],"additional_accession":[]},"is_claimable":false,"name":"Targeted Delivery of miR-34a via Anti-CD47 Antibody Conjugates for Enhanced Cancer Immunotherapy in Triple Negative Breast Cancer.","description":"Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that lacks estrogen receptor, progesterone receptor, and HER2 expression, which limits the efficacy of targeted therapies. MicroRNA-34a-5p (miR-34a), a tumor-suppressor miRNA known for regulating oncogenic pathways, initially appeared promising as a therapeutic avenue. However, the clinical translation of miR-34a has been hindered by challenges such as poor stability, inefficient cytoplasmic delivery, and immune-related toxicities, as evidenced by the failure of MRX34 in trials. To address these limitations, this study developes a novel antibody-oligonucleotide conjugate (AOC) platform anti-CD47-miR-34a conjugate (aCD47-C-miR34a). The aCD47-C-miR34a system combines the anti-CD47 antibodies with miR-34a using a bioreducible linker, ensuring targeted cytoplasmic delivery via CD47-mediated endocytosis and endosomal escape. CD47, an immune checkpoint protein overexpressed in TNBC, facilitates immune evasion, making it an attractive therapeutic target. In preclinical TNBC models, aCD47-C-miR34a successfully restored miR-34a's tumor-suppressive functions by downregulating oncogenic pathways including PD-L1, while modulating the tumor microenvironment. This dual mechanism promoted macrophage phagocytosis, enhanced CD8<sup>+</sup> T-cell activation, and induced apoptosis, resulting in significant tumor inhibition without systemic toxicity. These findings demonstrate the transformative potential of aCD47-C-miR34a in overcoming TNBC's oncogenic and immune-evasive mechanisms, paving the way for innovative treatments in TNBC and other heterogeneous, aggressive cancers.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-03T07:44:05.256Z","creation":"2026-04-26T03:09:45.443Z"},"accession":"S-EPMC12423919","cross_references":{"pubmed":["40692392"],"doi":["10.1002/smll.202504468"]}}