Novel, Self-Distinguished, Dual Stimulus-Responsive Therapeutic Nanoplatform for Intracellular On-Demand Drug Release

Abstract

On-demand drug release nanoplatforms are promising alternative strategies for enhancing the therapeutic effect of cancer chemotherapy. However, these nanoplatforms still have many drawbacks including rapid blood clearance, nontargeted specificity, and a lack of immune escape function. Even worse, they are also hindered via the dosage-limiting toxicity of traditional chemotherapeutic drugs. Herein, both dual-functional mannose (enhances the antitumor activity of chemotherapeutic drugs and exhibits an innate affinity against the lectin receptor) and amphiphilic d-α-tocopheryl polyethylene glycol 1000 succinate were selected to be covalently linked via a redox-responsive monothioether linkage. The synthesized self-distinguished polymer (TSM), as a structural motif, can be self-assembled into nanoparticles (TSM NPs) in an aqueous solution, in which doxorubicin (DOX) is loaded by weak interactions (TSM–DOX NPs). These TSM–DOX NPs can provide targeted, on-demand drug release under dual stimuli from lysosomal acidity and glutathione (GSH). In addition, TSM–DOX NPs can be self-distinguished via tumor cells in vitro and specifically self-distinguished from the tumor site in vivo. Further in vitro and in vivo research consistently demonstrated that TSM–DOX NPs display highly synergistic chemotherapeutic effects. Taken together, the data show that the self-distinguished GSH-responsive polymer TSM has the potential to load various therapeutic agents.

Shuttle-Shape Carrier-Free Platinum-Coordinated Nanoreactors with O2 Self-Supply and ROS Augment for Enhanced Phototherapy of Hypoxic Tumor

“…Physiological mediator stability is an important indicator in the biomedical application of nanodrugs . In addition, the dynamic coordination bond or weak intermolecular interactions within CPM contributed to the structural integrality of nanoreactors.…”

A nanodrug system overexpressed circRNA_0001805 alleviates nonalcoholic fatty liver disease via miR-106a-5p/miR-320a and ABCA1/CPT1 axis

“…With the development of nanotechnology, a large number of nanomaterials have been used as drug carriers in the biomedical field [ 43 , 44 ]. However, the entry of traditional nanomaterials into the body as exogenous substances leads to immune clearance and affects their bioavailability [ 45 ]. Moreover, some nanomaterials have the disadvantages of poor dispersion, poor stability and low drug loading rates [ 46 ].…”

On-Demand Drug-Delivery Platform Using Electrospun Nanofibers by Externally Triggered Glass Transition Switch

“…The development of on-demand drug release methods from polymer matrices has recently gained considerable attention. By making drug stimuli dependent, on-demand drug-delivery systems (DDSs) can explicitly control where, when, and how much of a drug is released with controlled release profiles and minimal off-target effects. , Various stimuli such as temperature, light, biomarkers, pH, magnetic field, electric field, and ultrasound have been used (alone or in combination) in on-demand DDSs. − The majority of conventional DDSs involve enteral routes, such as granules, capsules, and pills, while others involve parenteral delivery methods, such as subcutaneous, intramuscular, intravenous, or intra-arterial injection. − The routes and methods of administration have several disadvantages, including first-pass metabolism and discomfort. − Therefore, the development of a novel drug-delivery system is essential because it enables targeted drug administration while maintaining sustained and controlled release of drug throughout the treatment process.…”