Chunling Zhang, Min Tang, Ye Wu, Jiayi Lin, Jiyuan Zhang, Weidong Zhang, Bei Wang, Xin Luan
Microneedles (MNs) represent a minimally invasive transdermal drug delivery platform that has attracted considerable interest in pharmaceutical research owing to their ability to bypass the first-pass metabolism, maintain stable plasma drug levels, and improve bioavailability, safety, and patient compliance. Natural polysaccharides, as renewable biomaterials with low toxicity, excellent biocompatibility, and superior biodegradability, have emerged as promising candidates for MN fabrication. This review highlights recent advances in polysaccharide-based microneedles (PMNs) for cancer immunotherapy, with a particular focus on the structure-activity relationships of polysaccharides that influence MN performance, strategies for chemical modification to optimize mechanical and functional properties, state-of-the-art fabrication techniques such as 3D printing, and innovative cargo loading and delivery approaches. We also critically assess current limitations in polysaccharide characterization and clinical translation, proposing multidisciplinary strategies to overcome these bottlenecks. PMNs offer a compelling platform for enhancing microneedle biocompatibility, improving drug loading efficiency, and enabling more controlled and sustained drug release in cancer immunotherapy.