Reactive Oxygen Species Synergistic pH/H₂O₂-Responsive Poly(l-lactic acid)-block-poly(sodium 4-styrenesulfonate)/Citrate-Fe(III)@ZIF-8 Hybrid Nanocomposites for Controlled Drug Release

Abstract

Combination of photodynamic therapy and chemotherapeutic drugs is a promising strategy to achieve enhanced anticancer effect. In this study, a novel reactive oxygen species (ROS) synergistic pH/H2O2-responsive nanocomposite has been prepared from the self-assembly of poly­(l-lactic acid)-block-poly­(sodium 4-styrenesulfonate) in aqueous solution, followed by addition of ferric citrate (Cit-Fe­(III)) through electrostatic interaction and growing ZIF-8 among the surface of the particles. Upon H2O2 and visible light stimuli, efficient ROS such as hydroxyl radicals (•OH) and sulfate radicals (SO4 •–) can be generated through the catalyst of Cit-Fe­(III). Meanwhile, sulfonate-containing polymeric vesicles are disassembled through oxidization by ROS, and the encapsulated doxorubicin (DOX) will gradually diffuse into the ZIF-8 (one type of metal–organic framework, MOF) channels. The gatekeepers, ZIF-8, will collapse only under low pH condition, and a burst drug release is achieved. In the presence of H2O2 and pH stimuli upon visible light exposure, the prepared DOX-loaded nanocomposite exhibits good selectivity for both generating ROS and releasing drug in tumor cell instead of normal cell. The merits of nanocomposites such as good biocompatibility and especially the synergistic effect of chemo-photodynamic therapy make the material a highly promising candidate for drug delivery system in chemo-photodynamic therapy.

Light-Triggered Polymersome-Based Anticancer Therapeutics Delivery

“…As shown, the nanocomposite only combined chemotherapy and phototherapy in the presence of H 2 O 2 and pH stimuli upon visible light exposure. The prepared DOX-loaded nanocomposite exhibited good selectivity for generating ROS and releasing the drug in MCF-7 cells instead of 3T3-Swiss Albino cells (embryo fibroblast and normal cell) due to the higher concentration of H 2 O 2 and lower pH in tumor cells [ 306 ].…”

Stimulus-Responsive Nanomedicines for Disease Diagnosis and Treatment

“…Recently, pH/redox-responsive mixed polymeric micelles formed by self-assembly of two amphiphilic diblock copolymers (poly(ethylene glycol) methyl ether-b-poly(β-amino ester)) (mPEG-b-PAE) and poly(ethylene glycol) methyl ether-grafted disulfide bond-poly(β-amino ester) (PAE-ss-mPEG) have been developed, which released drugs at low pH and high GSH concentration in tumor cells [ 211 ]. In addition, there are also many combinations, such as pH/ROS responsive system [ 212 , 213 ], pH/enzyme responsive system [ 214 , 215 ] and others. As a significant characteristic stimulus condition in vivo, the combination of pH with other stimulus has shown promise for cancer treatments.…”

Zeolitic Imidazolate Framework Platform for Combinational Starvation Therapy and Oxygen Self-Sufficient Photodynamic Therapy against a Hypoxia Tumor

“…Owing to the large surface areas, tunable pore structures, and sizes of MOFs, they have been widely used in catalysis, gas adsorption, and biomedicines. − Recently, some research works have reported the encapsulation of photosensitizers by MOFs aiming to increase the delivery efficiency of photosensitizers to tumor sites for phototherapy, where the porous structure of MOFs minimizes the aggregation of photosensitizers. − Nevertheless, considering the complex tumor microenvironment, “smart” MOFs with tumor-specific stimuli-responsiveness are highly desirable. Among them, the zeolitic imidazolate framework (ZIF), as a typical MOF material, possesses the characteristics of endogenous acidic-responsiveness, − which enables itself not only to be transported to the tumor sites through the enhanced permeability and retention (EPR) effect , but also then to release the loaded photosensitizers in the acidic environment at tumor sites. Although several works have reported ZIFs as a “smart” platform to deliver and release photosensitizers for individual PDT, less research work has focused on ZIF-based nanoplatform loading with tumor-specific activated photosensitizers and other therapeutic agents for PDT-based combination therapy, particularly accompanied with highly efficient O 2 generation and hypoxia amelioration against a hypoxia tumor.…”