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Charge-reversal functionalized PLGA nanobubbles as theranostic agents for ultrasonic imaging-guided combination therapy

Abstract

The cancer chemotherapy efficacy can be generally restrained by the multiple drug resistance (MDR) of tumors, which is typically attributed to the up-regulation of ATP-binding cassette (ABC) transporter proteins such as P-glycoprotein (P-gp). It is an urgent requirement to present an innovative strategies to reverse MDR and enhance the therapeutic efficacy of chemotherapeutic agent in biomedical applications. Here, we reported a novel nanosystem of charge-reversal functionalized PLGA nanobubbles (denoted as Dox-NBs/PPP/P-gp shRNA) to co-delivery of Dox and P-gp shRNA for reversal of drug resistance and ultrasonic imaging-guided tumor therapy. The 1H-NMR, FT-IR, SEM, DLS and UV-vis spectrophotometer were conducted to characterize the structure, morphology and composition of the as-prepared nanobubbles. Dox-NBs/PPP/P-gp shRNA exhibited an average diameter of about 300 nm with good dispersity, biocompatibility and pH-responsive release property through the charge-reversal process. The in vitro experiments showed that Dox-NBs/PPP/P-gp shRNA nanobubbles can co-deliver Dox and P-gp shRNA into tumor cells and effectively suppress P-gp expression, leading to enhance the overall therapeutic effects against MCF-7/MDR cells by restraining the drug efflux. In vivo antitumor assay revealed that the approximately 65% inhibition rate of Dox-NBs/PPP/P-gp shRNA against MCF-7/ADR tumors in tumor-bearing nude mice. Both in vitro and in vivo toxicity results indicated Dox-NBs/PPP/P-gp shRNA are highly biocompatible with reducing side-effects and have ignorable systemic toxicity in vivo therapy of resistant cancers by combining with chemotherapeutic agent and P-gp knockdown. Furthermore, the in vivo imaging data substantiated that the functionalized nanobubbles can be used as an efficient contrast agent for ultrasonic imaging of solid tumors. This works highlighted the great potential of Dox-NBs/PPP/P-gp shRNA nanobubbles for enhanced imaging-guided combination therapy for overcoming MDR.

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Supplementary files

Publication details

The article was received on 17 Apr 2018, accepted on 10 Jul 2018 and first published on 12 Jul 2018


Article type: Paper
DOI: 10.1039/C8BM00419F
Citation: Biomater. Sci., 2018, Accepted Manuscript
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    Charge-reversal functionalized PLGA nanobubbles as theranostic agents for ultrasonic imaging-guided combination therapy

    H. Yang, X. Shen, J. Yan, X. Xie, Z. Chen, T. Li, S. Li, X. Qin, C. Wu and Y. Liu, Biomater. Sci., 2018, Accepted Manuscript , DOI: 10.1039/C8BM00419F

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