Understanding advanced poly (ethylene glycol)-disulphide-poly (lactic-co-glycolic acid) (PEG-SS-PLGA) nanoparticles for cutting-edge innovations, applications in smart drug delivery systems and targeted cancer therapy

Abstract Smart drug delivery technologies have become a revolutionary platform in cancer treatment and therapies by enabling precise, stimuli-responsive, and minimally toxic therapeutic interventions. Polyethene glycol-disulphide-poly(lactic-co-glycolic acid) (PEG-SS-PLGA) has received significant interest due to its redox-responsive disulphide functional groups, biodegradability, and ability to self-assemble into nanocarriers with adjustable physicochemical properties. The review provides an overall overview of PEG-SS-PLGA, beginning with its chemical structure, synthesis methods, and significant physicochemical properties. It highlights the use of disulphide bond cleavage in the tumour microenvironment, triggered by redox changes, with higher levels of glutathione, causing its release into the intracellular environment. This also addresses nanoparticle formulation methods, including drug encapsulation, kinetics of release, in vitro and in vivo performance, as well as applications ranging from monotherapy to co-delivery of chemotherapeutics, siRNA, and immunomodulators. Recent preclinical studies provide evidence of the potential to enhance therapeutic efficacy, reduce multidrug resistance, and offer theranostic imaging capabilities. The review concludes by integrating current knowledge, translational bottlenecks, and recommendations on future directions for optimising them, such as regulatory considerations, preclinical scalability, and incorporation into personalised oncology. Overall, PEG-SS-PLGA represents a promising future platform of targeted, responsive, and multifunctional cancer nanomedicine.