Drug -driven self-assembly of pH-sensitive nano-vesicles with high loading capacity and anti-tumor efficacy. (22nd March 2021)

• Record Type: Journal Article
• Authors: Zhai, Yaomin; Wang, Juan; Qiu, Liyan
• Is Part Of: Biomaterials science. Volume 9:Number 9(2021)
• Page Start: 3348
• Page End: 3361
• Publication Date: 2021-03-22
• Subjects: Biomedical materials -- Periodicals; 610.28
• DOI: 10.1039/d0bm01987a
• Languages: English
• ISSNs: 2047-4830

Abstract

Abstract : A pH-sensitive nano-vesicle was constructed by the drug-driven self-assembly of the amphiphilic copolymer PAP, which displayed a high drug loading capability of 35.77 wt% DOX·HCl and high tumor growth inhibition rate of up to 82.4% in mice. Abstract : The in vivo delivery of nanomedicine is severely hampered by the limited enhanced permeability and retention effect (EPR) in tumors. Aiming at overcoming this limitation and achieving high anti-tumor effect of chemotherapeutics, we specially addressed an available strategy from a viewpoint of increasing the drug loading of nano-carriers. Here, we constructed a novel pH-responsive polymersome based on the drug-driven self-assembly of amphiphilic polyphosphazenes PAP containing the ortho ester group ABD and mPEG2000 . Due to the non-covalent attractive forces between PAP and doxorubicin hydrochloride (DOX·HCl), DOX·HCl can induce the self-assembly of PAP via embedding itself in the lamella to form vesicles and the subsequent location in the center aqueous chamber of the resultant nano-vesicles, which resulted in the high drug loading content of 35.77 wt%. In addition, with the incorporation of cholesteryl hemisuccinate (CholHS), the premature leakage of DOX·HCl was significantly inhibited under physiological conditions. Meanwhile, the pH-sensitive drug release occurred at pH 5.5 by the advantage of the pH-sensitive biodegradation of ABD in PAP. Consequently, this CholHS-incorporated DOX·HCl-driven PAP vesicle achieved excellent anti-tumor effect with tumor growth inhibition up to 82.4% in S180 tumor-bearing mice. Taken together, our newly developed drug-driven vesicles may promote the development of efficient drug delivery systems for application in cancer therapy.