Smart microneedles for precision oncology: Bridging immunotherapy, biosensing, and AI-driven drug delivery

Cancer therapy increasingly requires drug-delivery strategies capable of improving spatial and temporal control of therapeutic exposure while limiting systemic toxicity. Microneedle (MN) technology has emerged as a versatile platform for localized and minimally invasive delivery of selected therapeutic agents, with applications investigated in cancer immunotherapy, nucleic-acid delivery, biosensing, and precision drug delivery. This review critically examines the current development of MN-based platforms in precision oncology, with emphasis on MN architecture, fabrication, therapeutic payloads, anatomical route, tumor accessibility, and mechanisms of controlled or stimuli-responsive delivery. We systematically evaluate MN architectures-solid, coated, hollow, dissolving, hydrogel-forming, and bioresponsive, alongside fabrication strategies including photolithography, micromolding, 3D printing, and laser ablation, contextualizing their drug-loading capabilities for fragile cargoes including immune checkpoint inhibitors (anti-PD-1, anti-PD-L1, anti-CTLA-4), cancer vaccines, mRNA constructs, siRNA, and patient-specific neoantigens. Preclinical studies indicate that selected MN-mediated delivery systems can increase local drug deposition, prolong intratumoral or tissue retention, modulate tumor-associated immune responses, and improve tumor-control outcomes in specific experimental models. However, these findings remain heterogeneous and are predominantly derived from cell-based and animal studies; they should therefore be interpreted as preclinical proof-of-concept rather than clinically validated evidence of superior efficacy or safety. Comparative performance depends on tumor location, MN architecture, payload, dose, administration route, release kinetics, and the comparator treatment. This review therefore emphasizes the distinction between experimental efficacy and clinical translation, with particular attention to pharmacokinetics, local versus systemic exposure, tumor accessibility, manufacturing reproducibility, safety, regulatory requirements, and patient-specific factors. Crucially, this review highlights the convergence of MNs with integrated biosensors and AI-driven closed-loop systems capable of real-time tumour microenvironment surveillance and adaptive drug release, a transition from passive carrier to active therapeutic agent. Special attention is given to bioresponsive MNs exploiting pH, enzymatic, and redox signals within the immunosuppressive tumour microenvironment, and to applications in paediatric and geriatric oncology where minimally invasive delivery addresses critical unmet needs. Outstanding barriers, restricted drug-loading capacity, fabrication scalability, long-term biocompatibility, and regulatory ambiguity for drug-device combination products, are critically addressed alongside future research imperatives. As nanotechnology, immunotherapy, and artificial intelligence converge, MNs represent a promising but still predominantly preclinical platform whose clinical value will depend on demonstrating reproducible dosing, appropriate tumor access, safety, and meaningful advantages over established delivery strategies.