Recent Progress in Bio-Responsive Drug Delivery Systems for Tumor Therapy

Abstract

Spatially- and/or temporally-controlled drug release has always been the pursuit of drug delivery systems (DDSs) to achieve the ideal therapeutic effect. The abnormal pathophysiological characteristics of the tumor microenvironment, including acidosis, overexpression of special enzymes, hypoxia, and high levels of ROS, GSH, and ATP, offer the possibility for the design of stimulus-responsive DDSs for controlled drug release to realize more efficient drug delivery and anti-tumor activity. With the help of these stimulus signals, responsive DDSs can realize controlled drug release more precisely within the local tumor site and decrease the injected dose and systemic toxicity. This review first describes the major pathophysiological characteristics of the tumor microenvironment, and highlights the recent cutting-edge advances in DDSs responding to the tumor pathophysiological environment for cancer therapy. Finally, the challenges and future directions of bio-responsive DDSs are discussed.

Cyclodextrin-Based Polymeric Drug Delivery Systems for Cancer Therapy

“…In addition, the intracellular concentration (2–10 mM) of GSH is about ~1000 times higher than the extracellular environment (2–20 μM). Therefore, differences between tumor cells and normal cells as well as intracellular and extracellular environments facilitate the development of redox-responsive drug delivery systems [ 103 , 104 ]. Hu’s group synthesized a panel of redox-responsive supramolecular pseudoblock polycations (CD-SS-pDM/Ad-pPEGs), in which pDM (poly (2-dimethyl amino)ethyl methacrylate) was conjugated on β-CD core via a disulfide bond, and the resulting star-like CD-SS-pDM was complexed with adamantine-ended pEGEEMA (poly(poly(ethylene glycol)ethyl ether methacrylate)) through host–guest interaction.…”

Improvement of the Antioxidant and Antitumor Activities of Benzimidazole-Chitosan Quaternary Ammonium Salt on Drug Delivery Nanogels

“…Nanogels are exceptionally sensitive to diverse stimuli owing to their distinctive 3D structures. Acidosis, high levels of reactive oxygen species (ROS), redox reactions, hypoxia, special enzyme overexpression, and temperature are commonly employed as triggers to initiate structural changes in nanogels [19,[29][30][31][32][33]. The tumor microenvironment is characterized by acidosis, which is both a typical pathological and physiological feature.…”

Time-Separated Pulse Release–Activation of an Enzyme from Alginate–Polyethylenimine Hydrogels Using Electrochemically Generated Local pH Changes

“…In the last few decades, smart materials have gotten a lot of attention due to their application in the biomedical field. , In particular, on-demand (signal-triggered) release was extensively studied for drug delivery purposes. , Among the triggering factors, one can mention biomolecular signals, magnetic field, mechanical force, temperature, electromagnetic (such as visible light, infrared, and radio waves) radiation, ultrasound, electrical field, and even more sophisticated signals, like breath . One of the most usable triggers for drug delivery is pH , due to its endogenous nature, which is often associated with a certain disease.…”