作为传统口服和静脉注射的替代方法，具有有限功效，经皮给药（TDD）在肿瘤治疗中显示出了巨大的潜力。过去十年中，由于其出色的生物相容性、可降解性和易得性，天然高分子已被设计成各种纳米载体，为TDD提供了更多选择。此外，天然高分子的丰富功能基团的表面功能化改性，进而开发成具有靶向和刺激响应功能的材料，可以将药物精确地输送到肿瘤部位，并对特定刺激响应释放药物。这不仅提高了肿瘤的治疗效率，还减少了对正常组织的毒性和副作用。因此，基于天然高分子的TDD（NPTDD）系统在肿瘤疗法中具有巨大的潜力。本文综述了NPTDD系统的机制，如穿透增强剂、纳米颗粒、微针、水凝胶和由透明质酸、壳聚糖、海藻酸钠、纤维素、肝素和蛋白质制备的纳米纤维，并概述了它们在肿瘤疗法中的应用。本文还概述了NPTDD系统用于局部治疗肿瘤的未来前景和当前的挑战。© 2023 Wiley-VCH GmbH.

As an alternative to traditional oral and intravenous injections with limited efficacy, transdermal drug delivery (TDD) has shown great promise in tumor treatment. Over the past decade, natural polymers have been designed into various nanocarriers due to their excellent biocompatibility, biodegradability, and easy availability, providing more options for TDD. In addition, surface functionalization modification of the rich functional groups of natural polymers, which in turn are developed into targeted and stimulus-responsive functional materials, allows precise delivery of drugs to tumor sites and release of drugs in response to specific stimuli. It not only improves the treatment efficiency of tumor but also reduces the toxic and side effects to normal tissues. Therefore, the development of natural polymer-based TDD (NPTDD) systems has great potential in tumor therapy. In this review, the mechanism of NPTDD systems such as penetration enhancers, nanoparticles, microneedles, hydrogels and nanofibers prepared from hyaluronic acid, chitosan, sodium alginate, cellulose, heparin and protein, and their applications in tumor therapy are overviewed. This review also outlines the future prospects and current challenges of NPTDD systems for local treatment tumors.© 2023 Wiley-VCH GmbH.