Novel multi-sensitive pseudo-poly(amino acid) for effective intracellular drug delivery

Abstract

A novel intracellular pH, glutathione (GSH) and reactive oxygen species (ROS)-responsive nanoparticles were obtained using mPEG 2k -block-redox dual sensitive chain-block-mPEG 2k (PRDSP) which was prepared by Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) Click polymerization. The disulfide bond, peroxalate ester and triazole units were regularly and repeatedly arranged in the hydrophobic 10 blocks. The disulfide bond was GSH-sensitive and peroxalate ester structure could be disrupted by acid and hydrogen peroxide. In addition, triazole units are capable of forming pH-responsive hydrogen bonds. Dynamic Light Scattering (DLS) and Transmission electron microscopy (TEM) was used to investigate the pH, GSH and ROS sensitivity of PRDSP nanoparticles (NPs).The results indicated that the average diameter, size distribution and morphology greatly changed upon adding GSH /H 2 O 2 or modulating pH. 15 As the preloaded model anticancer drug, Doxorubicin (DOX) was quickly released from DOX-loaded PRDSP (PRDSP@DOX) NPs by addition of 10 mM Glutathione (GSH), 10 mM H 2 O 2 or under acidic condition rather than under physiological condition. Confocal laser scanning microscopy(CLSM) and flow cytometric analyses revealed that PRDSP@DOX could effectively deliver DOX into the cytoplasm and nucleus of cells. Therefore, PRDSP NPs may be a promising redox heterogeneity-sensitive carrier for 20 efficient and controlled anticancer drug release. 65 entirely destroyed, leading to a slow but incomplete drug release. Drug efficiency is another crucial point. High drug loading content (DLC) and drug loading efficiency (DLE) are commonly

Reactive‐Oxygen‐Species‐Responsive Drug Delivery Systems: Promises and Challenges

“…B) Preparation of DOX‐loaded PRDSP nanoparticles, their uptake and intracellular microenvironment triggered release of DOX. Reproduced with permission . Copyright 2015, Royal Society of Chemistry.…”

“…To increase the sensitivity of the peroxalate‐based nanoparticles, Wu et al synthesized a dual sensitive ABA‐type amphiphilic triblock polymer (PRDSP), wherein the middle hydrophobic block was incorporated with peroxalate ester units and disulfide bonds repeatedly, and PEGs were selected as outer hydrophilic blocks . The DOX‐loaded PRDSP nanoparticles showed accelerated release of DOX under biologically relevant concentration of glutathione (10 m m ) and H 2 O 2 (10 m m ) compared to the physiological conditions (Figure B).…”

Sensors, Imaging Agents, and Theranostics to Help Understand and Treat Reactive Oxygen Species Related Diseases

“…Kang and co‐workers developed H 2 O 2 reactive hydroxybenzyl alcohol‐based nanoparticles to effectively release fluorescent probes and drugs toward the application of imaging and therapy of ischemia‐reperfusion injury. More recently, Huang and co‐workers developed a self‐assembled delivery system for doxorubicin. The system was sensitive to H 2 O 2 , GSH and pH, and delivered the drug to cytoplasm and nucleus of cancer cells after cell endocytosis.…”

“…Images of doxorubicin and doxorubicin‐loaded delivery systems with or without GSH in HeLa cells to monitor drug release (right). Reproduced with permission . Copyright 2015, The Royal Society of Chemistry.…”

A Comprehensive Outlook of Synthetic Strategies and Applications of Redox‐Responsive Nanogels in Drug Delivery

“…ROS is an important indicator and a major characteristic of several pathological conditions, including cancer, where elevated intracellular levels have been reported in disease conditions . ROS‐responsive drug delivery carriers currently being developed mostly involve organochalcogens (selenium, tellurium, diselenium, and ditellurium), organoboron compounds (aryl boronic ester), sulfur containing compounds (thioether, thioketal, vinyl dithioether), aryl oxalates, and ferrocenes, either as cross‐linkers or as important constituents of polymeric backbone. Although very few studies have been reported for ROS‐responsive nanogels, it would be worthwhile to review some of the important reported results, due to the potential applicability of the ROS‐responsive units in the development of advanced redox‐responsive nanogel‐based systems in the near future.…”