Phenylboronic acid modification augments the lysosome escape and antitumor efficacy of a cylindrical polymer brush-based prodrug

Abstract

Timely lysosome escape is very important for nanomedicines to avoid premature degradation. Herein, we report an exciting finding that phenylboronic acid (PBA) modification can greatly facilitate the lysosome escape of cylindrical polymer brushes (CPBs), and further promote their exocytosis and transcellular transfer. This fundamental finding for the first time reveals that PBA groups improve the tumor penetration of nanomaterials via an active transcytosis mechanism. We speculate that the mechanism of the PBA-enhanced lysosome escape is associated with the specific interactions of the PBA group with the lysosomal membrane proteins and hot shock proteins. The featured advantage of the PBA modification over the known lysosome escape strategies is that it does not cause significant adverse effects on the properties of the CPBs. Furthermore, doxorubicin was conjugated to the PBA-modified CPBs with drug loading content larger than 20%. This CPBs-based prodrug could eradicate the tumors established in mice by multiple intravenous administration.

Transformable Magnetic Liquid-Metal Nanoplatform for Intracellular Drug Delivery and MR Imaging-Guided Microwave Thermochemotherapy

“…Timely endosome escape is very important for preserving the pharmacological activity of the endocytosed nanomedicines. 7 To further verify the destruction of the endosomal membrane by the MW-driven shape transformation, the intracellular behaviors of MLMAL NPs was visualized by TEM imaging (Figure 3d). Without MW exposure, MLMAL NPs fused with each other within the endosome and together with little single MLMAL NPs observed in the acidic endosomes (Figure S13).…”

“…6 However, they are prone to be degraded and destroyed after cellular uptake and consequent lysosomal sequestration on account of the acidic microenvironment and massive enzymes in the endosome, leading to the inactivation of drugs. 7,8 Hence, the timely escape of drug molecules in endosomes remains a major obstacle during drug therapy.…”