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Poly(lactobionamidoethyl methacrylate)-based amphiphiles with ultrasound-labile components in manufacture of drug delivery nanoparticulates for augmented cytotoxic efficacy to hepatocellular carcinoma

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Indexed by:期刊论文

Date of Publication:2019-09-01

Journal:JOURNAL OF COLLOID AND INTERFACE SCIENCE

Included Journals:SCIE、EI、PubMed

Volume:551

Page Number:1-9

ISSN No.:0021-9797

Key Words:Ultrasound; Drug delivery; Stimuli-responsive chemistry; Anti-tumor therapy; Polymeric nanoparticulates

Abstract:Ultrasound-responsive chemistry was exploited in manufacture of drug delivery nanoparticulates for pursuit of on-demand ultrasound-stimulated drug release function. In principle, the ultrasound-labile oxyl-alkylhydroxylamine (-oa-) linkage was tailored between the segments of amphiphiles. Consequently, the hydrophobic chemotherapeutic doxorubicin could be readily assembled with the hydrophobic segments of amphiphiles into interior compartments, whereas the hydrophilic segments represented as the external surroundings. Upon ultrasonication, the proposed phase-segregated self assemblies were determined to be subjected to evident structural rearrangement as a consequence of -oa- cleavage. Simultaneously, the release rate of doxorubicin payloads appeared to accelerate due to the ultrasound-induced structural destabilization, consequently eliciting potent cytotoxic efficacy at the affected cells. Another noteworthy characteristic of the proposed self-assemblies was poly (lactobion-amidoethyl methacrylate) (pLAMA) as the hydrophilic components of the amphiphiles, characterized to possess galactosylated residues. In view of the specific affinity of galactosylated residues (and lactosylated residues) to asialoglycoprotein receptors (overexpressed on the surface of intractable hepatocellular carcinoma), the proposed self-assemblies were determined to impart preferential affinities to hepatocellular carcinoma. Together with the strategic ultrasound-stimulated drug release property, our proposed drug delivery system demonstrated appreciably pharmaceutical efficacy on hepatocellular carcinoma. (C) 2019 Elsevier Inc. All rights reserved.

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