H₂O₂‐Responsive Organosilica‐Doxorubicin Nanoparticles for Targeted Imaging and Killing of Cancer Cells Based on a Synthesized Silane‐Borate Precursor

Abstract

Doxorubicin (Dox) is a widely used fluorescent chemotherapy drug. Its primary delivery systems, based on physical adsorption to silica nanoparticles, can lead to low drug loading. Direct loading of Dox via covalent bonds during the formation of silica nanoparticles has never been reported. In this work, we designed and synthesized a silane‐borate precursor, which contains not only an alkoxysilane moiety to form organosilica nanoparticles but also a phenylboronic acid moiety to react with diol‐containing compounds. Using this compound, the covalent loading of Dox during the preparation of organosilica nanoparticles was effectively realized with a high drug loading content up to 22.4 %. Further modification by hyaluronic acid (HA) bestowed the Si‐Dox@HA nanoparticles with the ability to target CD44‐overexpressing cancer cells. The Si‐Dox@HA nanoparticles exhibited H2O2‐responsive release of about 80 % Dox and displayed seven‐fold selectivity for killing cancer cells over normal cells, relative to Dox and Si‐Dox nanoparticles. Moreover, these Si‐Dox@HA nanoparticles are also suitable for targeted fluorescence imaging of CD44‐overexpressing cancer cells.

Real-time SERS monitoring anticancer drug release along with SERS/MR imaging for pH-sensitive chemo-phototherapy

“…In addition, the characteristic peaks at 1625 and 2910 cm ˗1 in GO-Fe 3 O 4 @Au@Ag-MPBA-DOX are assigned to C O stretching vibration and C–H stretching vibration of DOX. Although the interactions between boronic acids and diols of DOX have been verified by many studies 39 , 40 , 41 , thin-layer chromatography (TLC) and mass spectrometry (MS) were further performed to confirm their conjugation, where the new product MPBA-DOX in reaction solution can be found (Supporting Information Figs. S8 and S9 ).…”

Overview of stimuli-responsive mesoporous organosilica nanocarriers for drug delivery

“…Moreover, they also reported that this improved selectivity resulted in a superior cytotoxicity towards MDA-MB-435 cells, 60 % and 40 % of cell viability for the groups treated with DOX loaded MONs and DOX loaded Her2 affibody targeted MONs, respectively. Xu et al developed hyaluronic acid functionalized PMOs to perform the targeted chemotherapy of liver cancer [100]. The hyaluronic acid is the primary binding molecule of CD44, a glycoprotein overexpressed in various tumors such as breast, liver, and lung cancer.…”

Mechanism of action of an Ir(iii) complex bearing a boronic acid active as a H2O2-responsive photosensitizer: ROS generation and quinone methide release for GSH scavenging

“…32 For instance, aryl boronic acids and their esters are used as H 2 O 2 -responsive moieties owing to the ease of synthesis and good biocompatibility as the products of the reaction show no cytotoxicity and the reaction with H 2 O 2 is highly selective. [33][34][35][36] These prodrugs are designed to release quinone methide (QM) as a by-product, 30,32,37,38 which was reported to rapidly alkylate GSH, leaving cells defenceless from ROS, 38,39 thus allowing an enhancement of PDT efficacy.…”