2026-10-11T20:22:07Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34046963 2026-10-01T16:25:07Z category_4 category_146 category_12 category_13 category_14 category_19 category_21 category_873 category_64 category_128 category_132 category_133 category_134 portal_87 item_type_3 month_year_10_2026

Heat-preconditioned MSC-derived exosomal miR‑486‑5p reverses doxorubicin resistance in breast cancer Di Xu (1443394) Xiaoyan Xu (283959) Fei Deng (170132) Liping Dong (255033) Wei Zhang (405) Yang Wu (66682) Biochemistry Space Science Cell Biology Genetics Molecular Biology Pharmacology Biotechnology Chemical Sciences not elsewhere classified Cancer Hematology Infectious Diseases Plant Biology Virology Breast cancer chemoresistance mesenchymal stem cells (MSCs) exosomes heat preconditioning tumor spheroids <p>Objective: Drug resistance remains a major obstacle to chemotherapy in breast cancer. human bone marrow-derived mesenchymal stem cells (MSC)-derived exosomes are promising drug-delivery nanocarriers, but their anticancer efficacy is limited by insufficient cargo loading. We aimed to engineer MSC-derived exosomes with enhanced anti-resistance activity via mild heat preconditioning. Methods: MSCs were preconditioned at 41°C for 1 h (heat-preconditioned exosomes, HP-Exo) or at 37°C (non-heat-preconditioned exosomes, No HP-Exo). Exosome yield, stemness, and microRNA (miRNA) profiles were assessed. MCF-7/ADR doxorubicin (DOX)-resistant cells were cultured as three-dimensional (3D) spheroids and treated with HP-Exo or No HP-Exo with or without DOX; cell viability and apoptosis were evaluated. Results: Heat preconditioning preserved MSC stemness and increased exosome secretion via Rab27b upregulation. HP-Exo, but not No HP-Exo, sensitized MCF-7/ADR spheroids to DOX, enhancing apoptosis. HP-Exo delivered microRNA-486-5p (miR-486-5p), which directly targeted high mobility group AT-hook 1 (HMGA1), downregulating breast cancer resistance protein (BCRP) and P-glycoprotein (P-gp). miR-486-5p inhibition abrogated, and its mimic restored, this chemosensitizing effect. Conclusion: Mild heat preconditioning is a simple strategy to engineer MSC-derived exosomes with enriched tumor-suppressive microRNA cargo and enhanced chemosensitizing activity, offering a promising nanotherapeutic platform to overcome chemoresistance in breast cancer.</p> 2026-10-01T16:25:07Z Dataset Dataset 10.6084/m9.figshare.34046963.v1 https://figshare.com/articles/dataset/Heat-preconditioned_MSC-derived_exosomal_miR_486_5p_reverses_doxorubicin_resistance_in_breast_cancer/34046963 CC BY 4.0