Multi-Stimuli Responsive Nanoparticles: Next-Generation Platforms for Smart Drug Delivery

Stimuli-responsive nanoparticles (NPs) are a major improvement to standard drug delivery methods because these allow the release of therapeutic agents in response to a particular biological response. Individual-stimuli-responsive systems, designed to react to a single stimulus (pH, temperature, redox gradient, etc.), have been shown to make more therapeutic impact and less systemic toxicity than non-responsive preparations. Nevertheless, the heterogeneity and complexity of most disease microenvironments, like the concomitant gradients of pH, expression of enzymes, and hypoxia in solid tumors, frequently surpass the discriminative ability of a solitary stimulus. This may result in inappropriate targeting or the early release of drugs in non-diseased tissues that may also have the triggering condition. The use of multi-stimuli-responsive block copolymers in the nanomaterial system addresses the drawbacks of the single-stimuli-responsive system. This system surpasses the risk of off-target pharmaceutical release. These discharge encapsulated substance upon the presence of several cues, including low pH, high ROS, temperature, light, and the presence of intracellular enzymes, in a variety of biomedical conditions, including cancers, diabetes and metabolic disorders, autoimmune inflammatory diseases, neurological disorders and bacterial infections. The multi-stimulus-responsive NPs have increased activation potential due to their ability to be responsive to a variety of pathological cues related to the disease status, thus ensuring better therapeutic outcomes. Regardless of this heterogeneous promise, their clinical application poses significant challenges of dysregulated immune activation, biocompatibility, batch-to-batch variation, and the absence of standardized regulatory pathways.

The objective of the present review includes examining and considering the various forms of internal and external stimuli and their incorporation into one nanoplatform to treat a wide range of biomedical conditions. This review prominently emphasizes the design of various stimuli-responsive NPs along with their preparation techniques and regulatory hurdles for their clinical utilization.