Smart microneedle platforms for skin cancer therapy: a review of stimuli-responsive and targeted drug delivery systems.

Abstract

Skin cancer's rising global incidence and the significant limitations of conventional therapies, such as systemic toxicity and drug resistance, necessitate the development of more effective and personalised treatment strategies. The emergence of MN integrated, stimuli-responsive platforms as an advanced therapeutic approach for skin cancer offers to bypass the skin's primary barrier, the stratum corneum, enabling targeted, localised delivery of therapeutic agents. By incorporating 'smart' materials, these platforms can release their payload in response to specific endogenous stimuli within the tumour microenvironment (e.g. pH, enzymes, redox potential) or externally applied triggers (e.g. Light, Temperature, ultrasound). This allows for on-demand, controlled release, enhancing therapeutic efficacy while minimising systemic side effects. This review focuses on the synergistic integration of these technologies, analysing how they enable potent combination therapies. Preclinical studies have demonstrated the potent synergistic effects of these platforms, particularly in combining chemo, photothermal (PT), and immunotherapies, achieving high tumour inhibition rates in animal models. However, translation to clinical settings faces challenges, including drug loading capacity, mechanical reliability, scalable manufacturing, and complex regulatory pathways. Current clinical trials are cautiously validating simpler, single-agent MN systems for non-melanoma skin cancers. This review highlights that while significant hurdles remain, the integration of MNs with stimuli-responsive systems represents a powerful strategy, with future developments in theranostics and closed-loop systems poised to revolutionise personalised skin cancer therapy. Future developments in theranostics, wearable biosensors, and closed-loop feedback systems are poised to overcome current limitations, offering a forward-looking perspective on cost-effective, patient-centric treatments that can adapt to the evolving biology of the disease.