Natural polysaccharide-based microneedles: A promising frontier in cancer immunotherapy

Cancer immunotherapy involves harnessing the body's immune system to fight tumors; however, delivering treatments effectively and precisely remains a challenge. To that end, transdermal drug delivery via microneedles (MNs) offers a minimally invasive solution.

A new review in Glycoscience & Therapy focuses on a new material for these microneedles: natural polysaccharides. Derived from sources like plants, animals, and microbes, these sugars (e.g., hyaluronic acid, chitosan) are not only highly biocompatible and biodegradable but can also actively modulate the immune system.

The review distinguishes itself by positioning PMNs as an integrated “active therapeutic platform rather than passive drug carriers. The authors examined how PMNs function as both a delivery vehicle and an immunomodulator. They found that PMNs can transport various anti-cancer agents—from small molecules and antibodies to nanoparticles—directly into the skin, targeting rich networks of immune cells. Beyond simple delivery, the polysaccharide matrix itself can actively interact with and modulate these immune cells, creating a powerful dual-action therapy.

The review also detailed advances in material science, summarizes the unique structure-activity relationships of polysaccharides, their physicochemical properties tunability, and how these features can be exploited to improve mechanical strength, biocompatibility, controlled biodegradation, and tumor-specific responsiveness of MNs.

Overall, the review highlights three interconnected innovations at the materials–device interface:

1. Dual-Function Design: Intrinsic bioactivity of natural polysaccharides (e.g., chitosan-mediated interactions with dendritic cells) enables inherent immunomodulatory effects, generating synergistic responses alongside delivered anticancer agents.
2. Precision Manufacturing Frontier: Aadvanced fabrication, particularly 3D printing, plays a role in overcoming the structural and functional constraints of conventional microneedle manufacturing. Such approaches allow the rational design of geometrically customized MN architectures with improved mechanical performance, tissue interaction, and drug-loading capacity—key parameters for immunotherapy-oriented applications.
3. Engineering Microenvironment Responsiveness: The review synthesizes strategies for engineering PMNs that respond to tumor-associated cues, such as pH gradients or enzymatic activity, enabling localized and temporally controlled drug release. This materials-driven adaptability represents a clear conceptual advance over static, non-responsive MN systems.

Collectively, this materials-driven perspective positions PMNs as a versatile and scalable platform for next-generation cancer immunotherapy, providing a foundation for the rational design of intelligent drug–device combination systems in oncology.

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Contact the author: Xin Luan, State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Shanghai Frontiers Science Center of TCM Chemical Biology, Shuguang Lab of Future Health, Institute of Interdisciplinary Integrative Medicine Research and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, PR China, luanxin@shutcm.edu.cn

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