Microneedle‐Assisted Systems for the Delivery of Proteolysis Targeting Chimeras (PROTACs)

Cancer remains a major global health challenge with increasing incidence and mortality rates. While conventional therapies such as chemotherapy and radiotherapy are the standard, they often suffer from off‐target toxicity and resistance. Although the specificity of targeted therapies has improved, challenges such as drug resistance and adverse effects still persist. Proteolysis‐targeting chimeras (PROTACs) offer a novel approach by degrading rather than inhibiting these oncogenic proteins, which often have the potential to overcome resistance mechanisms. However, their clinical application is impeded by poor solubility, bioavailability, and inefficient tumor targeting. In response, microneedles (MNs) have emerged as an innovative transdermal delivery platform capable of localized, controlled, and minimally invasive drug administration. The ability of these MNs to enhance tissue penetration and drug retention makes them ideal for overcoming PROTAC delivery barriers in cancer. To provide context and evidence, relevant publications were collated from Google Scholar, PubMed, ScienceDirect, Dimensions AI, and EBSCO, using specific keywords such as “cancer,” “diagnosis,” “drug loading,” “drug transport,” “microneedles,” “PROTACs,” “protein degradation,” “transdermal drug delivery,” “targeted degradation,” and “ubiquitination”. We did not impose any restrictions on the publication date during the selection process of papers. However, it is imperative to underscore that the initial reports containing specified keywords began publication in 2016. MNs‐assisted delivery of PROTACs offers a groundbreaking strategy for targeted cancer therapy by enhancing drug stability, bioavailability, and tumor specificity. This platform enables precise, localized, and minimally invasive drug delivery, often facilitating the co‐delivery of synergistic agents and stimuli‐responsive release. When engineered with biomolecular targeting and smart sensing capabilities, these microneedles can optimize therapeutic efficacy while minimizing risks stemming from systemic toxicity. The ability of MNs to integrate diagnostics and therapeutics highlights their role in advancing personalized medicine. As research continues to evolve, microneedle‐enabled PROTAC delivery is poised to redefine cancer treatment paradigms, offering a highly adaptable, patient‐centric, and next‐generation therapeutic platform.