Portal de investigación
In Vivo Antitumor and Antimetastatic Efficacy of a Polyacetal-Based Paclitaxel Conjugate for Prostate Cancer Therapy
Fecha de publicación:
Fecha Ahead of Print:
Autores de CIPF
Participantes ajenos a CIPF
- Fernandez, Y
- Foradada, L
- Gimenez, V
- Garcia-Aranda, N
- Mancilla, S
- Borgos, SE
- Hyldbakk, A
- Bogdanska, A
- Gobbo, OL
- Prina-Mello, A
- Ponti, J
- Calzolai, L
- Nino-Pariente, A
- Paul, A
- Schwartz, S
- Abasolo, I
Grupos de Investigación
Abstract
Prostate cancer (PCa), one of the leading causes of cancer-related deaths, currently lacks effective treatment for advanced-stage disease. Paclitaxel (PTX) is a highly active chemotherapeutic drug and the first-line treatment for PCa; however, conventional PTX formulation causes severe hypersensitivity reactions and limits PTX use at high concentrations. In the pursuit of high molecular weight, biodegradable, and pH-responsive polymeric carriers, one conjugates PTX to a polyacetal-based nanocarrier to yield a tert-Ser-PTX polyacetal conjugate. tert-Ser-PTX conjugate provides sustained release of PTX over 2 weeks in a pH-responsive manner while also obtaining a degree of epimerization of PTX to 7-epi-PTX. Serum proteins stabilize tert-Ser-PTX, with enhanced stability in human serum versus PBS (pH 7.4). In vitro efficacy assessments in PCa cells demonstrate IC50 values above those for the free form of PTX due to the differential cell trafficking modes; however, in vivo tolerability assays demonstrate that tert-Ser-PTX significantly reduces the systemic toxicities associated with free PTX treatment. tert-Ser-PTX also effectively inhibits primary tumor growth and hematologic, lymphatic, and coelomic dissemination, as confirmed by in vivo and ex vivo bioluminescence imaging and histopathological evaluations in mice carrying orthotopic LNCaP tumors. Overall, the results suggest the application of tert-Ser-PTX as a robust antitumor/antimetastatic treatment for PCa.
Datos de la publicación
- ISSN/ISSNe:
- 2192-2640, 2192-2659
- Tipo:
- Article
- Páginas:
- -
- PubMed:
- 34706167
Advanced Healthcare Materials John Wiley and Sons Ltd
Citas Recibidas en Web of Science: 17
Documentos
- No hay documentos
Filiaciones
Keywords
- antitumor efficacy; nanomedicines; paclitaxel; pH-responsiveness; polyacetals; polymer-drug conjugates; prostate cancer
Financiación
Proyectos asociados
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