PEG-sheddable reduction-sensitive polyurethane micelles for triggered intracellular drug delivery for osteosarcoma treatment

In this study, PEG-sheddable reduction-sensitive polyurethane (SS-PU-SS-PEG) micelles were prepared for triggered intracellular drug delivery to improve the therapy efficacy of osteosarcoma. The SS-PU-SS-PEG micelles were about 80～90 ​nm in diameter and exhibited good biocompatibility and decent stability in PBS. In vitro drug release studies revealed that drug-loaded SS-PU-SS-PEG micelles released doxorubicin (DOX), a model drug used in this study, in a well-controlled fashion under a reductive environment. Nearly, 80% of the drug was released within 5 ​h. Intracellular release of DOX from the SS-PU-SS-PEG micelles increased upon incubation with the cells. The DOX micelles showed significant antitumour activity against Saos-2 ​cells, which was comparable with free DOX. Furthermore, the antitumour activity of DOX-loaded SS-PU-SS-PEG micelles was tested in vivo using Saos-2 cell-bearing xenograft tumour model. It was found that the DOX-loaded micelles exhibited markedly improved antitumour activity than free DOX. Together, findings from this study suggest that the SS-PU-SS-PEG micelles could help achieve well-controllable, reduction-triggered drug release and as a result ​could improve the antitumour efficacy of drugs for osteosarcoma treatment.
Source: Journal of Orthopaedic Translation - Category: Orthopaedics Source Type: research