Fluorescent boronate-based polymer nanoparticles with reactive oxygen species (ROS)-triggered cargo release for drug-delivery applications

Abstract

A new drug-delivery system of polymer nanoparticles (NPs) bearing pinacol-type boronic ester and alkyne moieties displaying triggered self-immolative polymer degradation in the presence of reactive oxygen species (ROS) with the capability of cellular imaging is presented. The NPs specifically release their drug cargo under concentrations of ROS that are commonly found in the intracellular environment of certain tumors and of inflamed tissues and exhibit significant cytotoxicity to cancer cells compared to their non-ROS-responsive counterparts.

Oxidation‐Responsive Materials: Biological Rationale, State of the Art, Multiple Responsiveness, and Open Issues

“…Response Mechanisms : Pinacol boronates (Figure A, left) are the gold standard: they combine good chemical stability at neutral pH, and a strong polarity change upon oxidation (hydrophobic to hydrophilic); this determines strong changes in (inter‐)molecular association. In many studies, however, the response is not solely based on the production of a phenol group, which is only an intermediate of a “self‐immolative” cascade based on a benzyl 1,6‐elimination.…”

“…In many studies, however, the response is not solely based on the production of a phenol group, which is only an intermediate of a “self‐immolative” cascade based on a benzyl 1,6‐elimination. In this mechanism, the phenol undergoes a rearrangement leading to the release of a p ‐quinone methide, or a cognate compound . The potential toxicity of these compounds is generally considered not to be an issue, since the p ‐quinone methide is expected to readily convert to p ‐hydroxybenzyl alcohol (HBA) upon reaction with water; however, it is not clear why they should be considerably less stable than the closely related o ‐quinone methides, which have half‐life times of at least a few hours in water, and show a similar reactivity, which includes DNA alkylation) and is employed in the design of ROS‐activated prodrugs .…”

“…The potential toxicity of these compounds is generally considered not to be an issue, since the p ‐quinone methide is expected to readily convert to p ‐hydroxybenzyl alcohol (HBA) upon reaction with water; however, it is not clear why they should be considerably less stable than the closely related o ‐quinone methides, which have half‐life times of at least a few hours in water, and show a similar reactivity, which includes DNA alkylation) and is employed in the design of ROS‐activated prodrugs . The advantageous features of the self‐immolative cascade include the higher hydrophilicity of the final structure (larger change in polarity), and the possibility to proceed further until the macromolecular backbone is cleaved (Figure B) with a recent example including the destabilization of a polyphosphazene backbone upon elimination of boronic acid and formation of an acid group on the backbone …”

ROS‐Sensitive Degradable PEG–PCL–PEG Micellar Thermogel

“…The retention time of the in vivo‐incubated polymer gel was observed at 15.3 min, which is between those of PBS and PBS containing 1.0 × 10 ‐3 m H 2 O 2 . The physiological concentration of H 2 O 2 is about 0.01–100 × 10 ‐6 m ; however, it increases by inflammation . Above 100 × 10 ‐6 m , H 2 O 2 might induce apoptosis of the cells .…”

Accelerated hydrolysis of boronic acid in a modified poly(amidoamine) dendrimer: identification of a factor leading to the production of an impurity in boronic acid containing poly(amidoamine) dendrimers

“…This equilibrium, also conceptualized as involving dynamic covalent bonds, is the foundation of various responsive materials, that is materials that interact with and selectively respond to the environment for various purposes, such as the specific delivery of cargo. 11 Moreover, alongside other types of dynamic covalent bonds, boronate-based functional materials can be tailored to respond to different types of environmental irradiation, making them suitable for diverse applications. 12…”