Doxorubicin-Loaded Polymeric Meshes Prevent Local Recurrence after Sarcoma Resection While Avoiding Cardiotoxicity.

Autor:	Bressler EM; Department of Biomedical Engineering, Boston University, Boston, Massachusetts., Chu NQ; Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Sabatelle RC; Department of Biomedical Engineering, Boston University, Boston, Massachusetts., Mahvi DA; Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Korunes-Miller JT; Department of Biomedical Engineering, Boston University, Boston, Massachusetts., Nagashima F; Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Ichinose F; Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Liu R; Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Grinstaff MW; Department of Biomedical Engineering, Boston University, Boston, Massachusetts.; Department of Chemistry, Boston University, Boston, Massachusetts., Colson YL; Division of Thoracic Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts., Raut CP; Department of Surgery, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2022 Dec 02; Vol. 82 (23), pp. 4474-4484.
DOI:	10.1158/0008-5472.CAN-22-0734
Abstrakt:	Surgery is the only potentially curative treatment for localized soft-tissue sarcomas. However, for sarcomas arising in the retroperitoneum, locoregional recurrence rates are 35% to 59% despite resection. Doxorubicin (DOX) is the standard first-line systemic chemotherapy for advanced soft-tissue sarcoma, yet its intravenous administration yields limited clinical efficacy and results in dose-limiting cardiotoxicity. We report the fabrication and optimization of a novel electrospun poly(caprolactone) (PCL) surgical mesh coated with layers of a hydrophobic polymer (poly(glycerol monostearate-co-caprolactone), PGC-C18), which delivers DOX directly to the operative bed following sarcoma resection. In xenograft models of liposarcoma and chondrosarcoma, DOX-loaded meshes (DoM) increased overall survival 4-fold compared with systemically administered DOX and prevented local recurrence in all but one animal. Importantly, mice implanted with DoMs exhibited preserved cardiac function, whereas mice receiving an equivalent dose systemically displayed a 23% decrease from baseline in both cardiac output and ejection fraction 20 days after administration. Collectively, this work demonstrates a feasible therapeutic approach to simultaneously prevent post-surgical tumor recurrence and minimize cardiotoxicity in soft-tissue sarcoma. Significance: A proof-of-principle study in animal models shows that a novel local drug delivery approach can prevent tumor recurrence as well as drug-related adverse events following surgical resection of soft-tissue sarcomas. (©2022 American Association for Cancer Research.)
Databáze:	MEDLINE
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