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

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 (lactobionamidoethyl 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.

• Authors: Jingyun Wang, Ying Xia, Huiying Liu, Jing Xia, Ming Qian, Liuwei Zhang, Lili Chen, Qixian Chen
• Journal: Journal of colloid and interface science (J Colloid Interface Sci) Vol. 551 Pg. 1-9 (Sep 01 2019) ISSN: 1095-7103 [Electronic] United States
• PMID: 31071490 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Hydroxylamines
• Polymethacrylic Acids
• Doxorubicin
• Galactose

Topics

• Antineoplastic Agents (administration & dosage)
• Carcinoma, Hepatocellular (drug therapy)
• Cell Survival (drug effects)
• Doxorubicin (administration & dosage)
• Drug Carriers (chemistry)
• Drug Liberation
• Galactose (chemistry)
• Hep G2 Cells
• Humans
• Hydrophobic and Hydrophilic Interactions
• Hydroxylamines (chemistry)
• Kinetics
• Liver Neoplasms (drug therapy)
• Nanoparticles (chemistry)
• Polymerization
• Polymethacrylic Acids (chemistry)
• Ultrasonic Waves