Comparing the therapeutic potential of thermosensitive liposomes and hyperthermia in two distinct subtypes of breast cancer
| Autor: | Michiel Bolkestein, Wouter J.M. Lokerse, Simone U. Dalm, Alexander M.M. Eggermont, Gerben A. Koning, Marion de Jong, Holger Grüll |
|---|---|
| Přispěvatelé: | Surgery, Radiology & Nuclear Medicine |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Combination therapy Pharmaceutical Science Breast Neoplasms Pharmacology Polyethylene Glycols 03 medical and health sciences Mice 0302 clinical medicine Breast cancer SDG 3 - Good Health and Well-being In vivo Cell Line Tumor medicine Tumor Microenvironment Animals Humans Doxorubicin Breast Tumor microenvironment Mice Inbred BALB C Antibiotics Antineoplastic business.industry Cancer Hyperthermia Induced medicine.disease Combined Modality Therapy 030104 developmental biology 030220 oncology & carcinogenesis Delayed-Action Preparations Drug delivery Liposomes Female business Ex vivo medicine.drug |
| Zdroj: | Journal of Controlled Release, 258, 34-42. Elsevier |
| ISSN: | 0168-3659 |
| Popis: | Local drug delivery of Doxorubicin (Dox) with thermosensitive liposomes (TSL) and hyperthermia (HT) has shown preclinically to achieve high local drug concentrations with good therapeutic efficacy. Currently, this is clinically studied for treatment of chest wall recurrence of breast cancer, however with various outcomes. This study examines the potency of neoadjuvant TSL HT combination therapy in two orthotopic mouse models of human breast cancer, MDA-MB-231 and T-47D, which morphologically correlate to mesenchymal and epithelial phenotypes, respectively. Both cell lines showed improved in vitro chemosensitivity and Dox uptake at HT. Dox-loaded TSL (TSLDox) was stable in vitro in FBS, BALB/c-nu plasma and human plasma, although release of the drug at HT was incomplete for the latter two. Combination treatment with TSLDox and HT in vivo was significantly more effective against MDA-MB-231 tumors, whereas T-47D tumors showed no significant therapeutic response. Ex vivo investigation revealed a higher mean vessel density and poorly differentiated extracellular matrix (ECM) in MDA-MB-231 tumors relative to T-47D tumors. Although in vitro results of the TSLDox and HT treatment were favorable for both cell types, the therapeutic efficacy in vivo was remarkably different. The well-differentiated and slowly-growing T-47D tumors may provide a microenvironment that limits drug delivery to the target cell and therefore renders the therapy ineffective. Mesenchymal and invasive MDA-MB-231 tumors display higher vascularization and less mature ECM, significantly enhancing tumor response to TSLDox and HT treatment. These results yield insight into the efficacy of TSL treatment within different tumor microenvironments, and further advance our understanding of factors that contribute to heterogeneous therapeutic outcomes in clinical trials. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect