Living therapeutics approaches that exploit mesenchymal stem cells (MSCs) as nanomedicine carriers are highly attractive due to MSCs native tropism toward the 3D tumor microenvironment. However, a streamlined pre-clinical evaluation of nano-in-cell anti-cancer therapies remains limited by the lack of in vitro testing platforms for screening MSCs-3D microtumor interactions. Herein we generated dense breast cancer mono and heterotypic 3D micro-spheroids for evaluating MSCs-solid tumors interactions and screen advanced nano-in-MSCs therapies. Breast cancer monotypic and heterotypic models comprising cancer cells and cancer associated fibroblasts (CAFs) were self-assembled under controlled conditions using the liquid overlay technique. The resulting microtumors exhibited high compactness, reproducible morphology and necrotic regions, similarly to native solid tumors. For evaluating tumoritropic therapies in organotypic tumor-stroma 3D models, theranostic polydopamine nanoparticles loaded with indocyanine green-doxorubicin combinations (PDA-ICG-DOX) were synthesized and administered to human bone-marrow derived MSCs (hBM-MSCs). The dual-loaded PDA nano-platforms were efficiently internalized, exhibited highly efficient NIR-light responsivity and assured MSCs viability up to 3 days. The administration of PDA-ICG-DOX nano-in-MSC tumoritropic units to microtumor models was performed in ultra-low adhesion surfaces for simulating in vitro the stem cell-tumor interactions observed in the in vivo scenario. Bioimaging analysis revealed hBM-MSCs adhesion to 3D cancer cells mass and MSCs-chemo-photothermal nanotherapeutics exhibited higher anti-tumor potential when compared to their standalone chemotherapy treated 3D tumor counterparts. Overall, the proposed methodology is suitable for evaluating MSCs-microtumors individualized interactions and enables a rapid high-throughput screening of tumoritropic therapies bioperformance.
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http://dx.doi.org/10.1016/j.jconrel.2020.12.054 | DOI Listing |
Sci Rep
December 2024
Department of Clinical Pharmacy, Baoshan Hospital Affiliated to, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
This study investigates the potential treatment of breast cancer utilizing Gentiana robusta King ex Hook. f. (QJ) through an integrated approach involving network pharmacology, molecular docking, and molecular dynamics simulation.
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December 2024
Department of Breast Surgery, Second Affiliated Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, China.
Early prediction of patient responses to neoadjuvant chemotherapy (NACT) is essential for the precision treatment of early breast cancer (EBC). Therefore, this study aims to noninvasively and early predict pathological complete response (pCR). We used dynamic ultrasound (US) imaging changes acquired during NACT, along with clinicopathological features, to create a nomogram and construct a machine learning model.
View Article and Find Full Text PDFMetaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy of taxane. We report that NOS blockade potentiated response of human MpBC cell lines and tumors to phosphoinositide 3-kinase (PI3K) inhibitor alpelisib and taxane.
View Article and Find Full Text PDFthe evolution of axillary management in breast cancer has witnessed significant changes in recent decades, leading to an overall reduction in surgical interventions. There have been notable shifts in practice, aiming to minimize morbidity while maintaining oncologic outcomes and accurate staging for newly diagnosed breast cancer patients. These advancements have been facilitated by the improved efficacy of adjuvant therapies.
View Article and Find Full Text PDFthe axillary reverse mapping (ARM) procedure aims to preserve the lymphatic drainage structures of the upper extremity during axillary surgery for breast cancer, thereby reducing the risk of lymphedema in the upper limb. Material and this prospective study included 57 patients with breast cancer who underwent SLNB and ARM. The sentinel lymph node (SLN) was identified using a radioactive tracer.
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