RT Journal Article
T1 Cancer cell membrane-modified Soluplus® micelles for gemcitabine delivery to pancreatic cancer using a prodrug approach
A1 Pereira Silva, Miguel
A1 Díaz Gómez, Luis
A1 Blanco Fernández, Bárbara
A1 Ferreirós, Alba
A1 Veiga, Francisco
A1 Concheiro Nine, Ángel Joaquín
A1 Santos, Ana Cláudia Paiva
A1 Álvarez Lorenzo, Carmen
K1 Polymeric micelle
K1 Soluplus®
K1 Pancreatic cancer
K1 Gemcitabine
K1 Prodrug delivery
K1 Cancer cell membrane modification
AB Pancreatic cancer (PC) is one of the most lethal malignancies worldwide and its incidence is increasing. Chemotherapy is often associated to limited efficacy, poor targeting and systemic toxicity. In this work, the hydrophilic gemcitabine (GEM), widely used in PC treatment alone or in combination, was conjugated with vitamin E succinate (VES) and encapsulated in Soluplus® micelles. This prodrug approach facilitated encapsulation of the anticancer drug into the self-assembled copolymer micelles. Soluplus®/VES-GEM micelles were optimized regarding the ratio of the components and the preparation process. The micelles were small-sized (<80 nm), monodisperse, and highly stable, efficiently retaining the conjugate drug and showing significant antiproliferative activity against BxPC3 cell line. To improve biofunctionalization and targeting properties of prepared Soluplus®/VES-GEM micelles, biomimetic modification with PC cell membrane was further attempted by co-extruding PC cell membrane (BxPC3) nanovesicles with Soluplus®/VES-GEM micelles. Several protocols were attempted to prepare the BxPC3-modified Soluplus®/VES-GEM micelles and the outcomes were analyzed in detail. Overall, the results pave the way to innovative PC-targeted nanotherapies by maximizing GEM encapsulation in hydrophobic compartments with high stability and affinity. The results also highlight the need of higher resolution techniques to characterize cell membrane coating of nanocarriers bearing highly hydrophilic shells.
PB Elsevier
SN 0378-5173
YR 2024
FD 2024-07-30
LK https://hdl.handle.net/10347/39837
UL https://hdl.handle.net/10347/39837
LA eng
NO Pereira-Silva, M., Diaz-Gomez, L., Blanco-Fernandez, B., Ferreirós, A., Veiga, F., Concheiro, A., Paiva-Santos, A. C., & Alvarez-Lorenzo, C. (2024). Cancer cell membrane-modified soluplus® micelles for gemcitabine delivery to pancreatic cancer using a prodrug approach. International Journal of Pharmaceutics, 66210.1016/j.ijpharm.2024.124529
NO This work received financial support from grant FCT SFRH/BD/148771/2019 by the Fundação para a Ciência e Tecnologia (FCT, Portugal). The work was also partially supported by the Ministerio de Ciencia e Innovación MCIN/AEI/10.13039/501100011033 [PID2023-150422OB-I00] (Spain) and FEDER.
DS Minerva
RD 28 abr 2026