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Zwitterionic Strategy to Stabilize Self-immolative Polymer Nanoarchitecture Under Physiological pH for Drug Delivery In vitro and In vivo.
Advanced Healthcare Materials 2024 April 5
The major bottleneck in employing polymer nano-vectors for biomedical application, particularly those based on self-immolative poly(amino ester) (PAE)s lies in their uncontrolled auto-degradation at physiological pH before they can reach the intended target. Here, an elegant triblock-copolymer strategy is designed to stabilize the unstable PAE chains via zwitterionic interactions under physiological pH (pH 7.4) and precisely program their enzyme-responsive biodegradation specifically within the intracellular compartments, ensuring targeted delivery of the cargoes. To achieve this goal, biodegradable polycaprolactone (PCL) platform is chosen, and structure-engineered several di-and triblock architectures to arrive the precise macromolecular geometry. The hydrophobic-PCL core and hydrophilic anionic-PCL block at the periphery shielded PAEs against auto-degradation, thereby ensuring stability under physiological pH in PBS, FBS, cell culture-medium and blood-stream. The clinical anticancer drug doxorubicin and deep-tissue penetrable near-infrared IR-780 biomarker is encapsulated to study their biological actions by in vitro live-cancer cells and in vivo bioimaging in live-animals. These zwitterions are biocompatible, non-hemolytic, and real-time in vitro live-cell confocal studies have confirmed their internalization and enzymatic-biodegradation in the endo-lysosomal compartments to deliver the payload. In vivo bioimaging established their prolonged blood-circulation for over 72 h, and the biodistribution analysis revealed the accumulation of nanoparticles predominantly in the excretory organs. This article is protected by copyright. All rights reserved.
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