Thermally self-assembled biodegradable poly(casein-g-N-isopropylacrylamide) unimers and their application in drug delivery for cancer therapy

CUGGINO, JULIO C.; NICOLA, MARIBEL; CALDERÓN, MARCELO; AMBROSIONI, FRANCO E.; JIMÉNEZ KAIRUZ, ÁLVARO F.; MINARI, ROQUE J.; GUGLIOTTA, LUIS M.; PICCHIO, MATÍAS L.; GATTI, GERARDO; ALVAREZ IGARZABAL, CECILIA I.

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

ELSEVIER SCIENCE BV

Año: 2020 vol. 154 p. 446 - 455

0141-8130

In this work, we report the synthesis of graft copolymers based on casein and N-isopropylacrylamide, which can self-assemble into biodegradable micelles of approximately 80 nm at physiological conditions. The obtained copolymers were degraded by trypsin, an enzyme that is overexpressed in several malignant tumors. Moreover, graft copolymers were able to load doxorubicin (Dox) by ionic interaction with the casein component. In vitro release experiments showed that the in situ assembled micelles can maintain the cargo at plasma conditions but release Dox immediately after their exposition at pH 5.0 and trypsin. Cellular uptake and cytotoxicity assays revealed the efficient delivery to the nucleus and antiproliferative efficacy of Dox in the breast cancer cell line MDA231. Both delivery and therapeutic activity were enhanced in presence of trypsin. Overall, the prepared micelles hold a great potential for their utilization as dual responsive trypsin/pH drug delivery system.