Micro- and nanoformulations to induce apoptosis in cancer: A review

Therapeutic strategies to promote tumor cell apoptosis have been central features of clinical oncology for more than two decades. Although the BCL-۲ family and death receptor machinery have offered clinical opportunities (such as the FDA-approved BCL-۲ inhibitor venetoclax), there are some barriers that remain to be overcome. Traditional apoptotic modulators are often constrained by dose-limiting toxicities that can restrict the development of these compounds, suboptimal pharmacokinetics, and ultimately the development of resistance mechanisms, including target-site mutations or up-regulation of alternate survival pathways like MCL-۱. The current review aims to provide an overview of the molecular profile of apoptotic targets and the emerging reliance placed on micro- and nano-formulations to alleviate clinical drawbacks. We describe the intrinsic and extrinsic pathways as targets for intervention and review the availability of small-molecule inhibitors, TRAIL receptor agonists, and p۵۳ reactivators. Critically, we have placed nanotechnology not only to facilitate the delivery of therapeutics via passive targeting and active ligand conjugation, but also as a platform enabling precision-targeted agents. We also describe the possibility of multi-drug co-delivery systems for the simultaneous blockade of primary and escape pathways, and conclude with a discussion on stimuli-responsive smart formulations capable of inducing reprogramming of the tumor microenvironment to promote immunogenic cell death. With the incorporation of functional diagnostics tools such as BH۳ profiling together with pharmaceutical engineering, micro- and nano-formulations are predicted to convert apoptosis induction from a successful therapeutic strategy into an accurate, sustainable, and selective clinical destination for patients suffering from aggressive and refractory cancers.

کلیدواژه ها:

Cancer therapy ، Drug Delivery ، Nanoparticles ، Programmed Cell Death