Triple-responsive targeted hybrid liposomes with high MRI performance for tumor diagnosis and therapy

Targeted multi-responsive drug delivery systems with magnetic resonance imaging (MRI) capacity were anticipated as a promising tool for tumor therapy and diagnosis. Herein, we successfully synthesized anisamide-modified and non-modified UV/GSH-responsive molecules (10,10-NB-S-S-P-AA and 10,10-NB-S-S-P-OMe), and celecoxib-modified and non-modified UV/H2O2-responsive molecules (10,10-NB-OA-P-CE and 10,10-NB-OA-P-OMe). The targeted MRI-tracing UV/GSH/H2O2 triple-responsive hybrid liposomes (GNSOPAC) were fabricated by mixing with contrast agent (12,12-NB-DTPA-Gd), 10,10-NB-S-S-P-AA, and 10,10-NB-OA-P-CE in an optimal ratio of 6 : 1 : 1. GNSOPAC liposomes presented high DEE (>60%), favorable stability, good biocompatibility, and superior MRI performance. By MR imaging and fluorescence distribution in vivo, targeted drug-loaded liposomes (GNSOPACD) exhibited superior targeting activity than non-targeted drug-loaded liposomes (GNSOPMD) in the in vitro and in vivo studies. Compared with doxorubicin hydrochloride (DOX center dot HCl), the treatment of GNSOPACD + UV achieved a better anticancer effect in the in vitro and in vivo study, which may be related to the combined action of DOX center dot HCl, the celecoxib moiety and photolysis products. Moreover, GNSOPACD + UV exhibited negligible adverse effects during the in vivo treatment. Hence, anisamide and celecoxib co-modified UV/GSH/H2O2 triple-responsive hybrid liposomes with high MRI performance can act as a potential drug delivery system for tumor theranostics.

Automated summary

Targeted multi-responsive drug delivery systems with MRI capabilities were successfully synthesized, showing high stability and biocompatibility in vivo with excellent drug targeting effects.