Ovarian cancer (OC) is one of the most common malignant tumors of the reproductive tract in women, with the third morbidity and the highest mortality of all gynecologic malignancies [1,2]. Approximately 70 % of OC are diagnosed at stage III or IV, with five-year survival rates below 45 % [3,4]. The incidence and mortality of OC rates increase with age, and there are 239,000 new cases and 152,000 deaths from OC each year worldwide, which seriously threaten the life and health of women [5]. In clinical practices, although surgery is the cornerstone of treatment, it is rarely beneficial curative for patients with advanced OC [6]. Chemotherapy is a frequently employed therapeutic modality, alongside surgical intervention, in the management of ovarian cancer (OC). Chemotherapeutic agents such as carboplatin, cisplatin, paclitaxel, and bevacizumab are prescribed at various stages of OC. Unfortunately, the emergence of systemic toxicity substantially diminish the efficacy and security of these agents [7]. Furthermore, targeted molecular inhibitors tend to lose efficacy in the face of drug-resistant or metastatic ovarian cancer cells or when patients experience intolerable adverse effects [8]. Hence, there is a pressing need to explore alternative therapeutic strategies for OC that are both effective and characterized by minimal toxicity.

Microneedles (MNs), as an emerging transdermal drug technology, can help enhance the drug's delivery efficiency and overcome the problem associated with conventional formulations that are unable to directly reach the site of action [9]. MNs patch, a prominent strategy for local or systemic disease, widely applied to dermal vaccination, wound healing, especially cancer, has drawn much attention for clinicians [[10], [11], [12]]. It is different from oral administration, which can help the drug molecules circumvent the first-pass metabolism and gastrointestinal degradation to maximize the effectiveness of drugs [13]. In addition, MNs patches may play diversified roles when loaded with various material, such as employing magnesium microparticles loaded within the microneedle patch, for deeper and faster intradermal payload delivery [14], black phosphorus MNs patches with dual traditional Chinese medicine integration, to active the delivery systems quickly and controllably by photothermal regulation [15]. MNs patches have evolved beyond their initial scope of addressing superficial malignancies and diseases. Significant advancements have been achieved in treating internal diseases, such as glioblastoma and pancreatic cancer. For example, self-degradable MN patches have been developed to enable the controlled and sustained delivery of aPD1 for melanoma therapy [16]. MNs patch-loading cisplatin and IR820 (photosensitizer) was prepared to perform chemo-photodynamic therapy against breast cancer [17]. Glioblastoma was treat by MNs patch with on-demand multidrug delivery to the brain [18]. However, MNs patch are seldom integrated with traditional Chinese medicine, restricting their practical values.

Ginseng, a typical Chinese medicinal plant, has been used in medical fields for thousands of years. Notably, ginseng and ginsenosides show great anticancer potential, including suppressing tumor growth, invasion, and metastasis, and regulating tumor-associated immune responses [19]. Ginsenoside RG3, derived from Panax ginseng and Panax japonicus var, has been widely studied to conquer tumors [20]. Compared with other ginsenoside (like RG1, RG3, and RG5), RG3 can uniquely inhibit pre-mitotic protein and ATP synthesis in cancer cells. At the same time, the system toxicity hinders the application in the clinic. Thus, a new method, MNs patch loading traditional Chinese medicine, that would target the tumor tissue, enhance drug delivery, is still anticipated.

Herein, we developed a hydrogel microneedle patch for transdermal delivery of ginsenoside RG3 to treat OC safely and effectively. Gelatin methacryloyl (GelMA) hydrogel has the advantages of biocompatibility, biodegradability, non-cytotoxicity, and non-immunogenicity [21], and we produced the RG3-MNs with ginsenoside RG3-GelMA needle tips and 2-hydroxy-2-methylpropiophenone-hydrogel needle bottom. Due to their micron-scale dimensions and exceptional drug-loading efficiency, MNs patches offer the advantage of achieving optimal anticancer therapy. This is achieved by ensuring that drugs accumulate therapeutically effective concentrations at the intended target site while minimizing side effects [16,22,23]. Given the maneuverability of ginsenoside RG3-MNs (RG3-MNs), we testified the drug release efficiencies and anticancer efficiency in vivo and in vitro that prove the feasibility of RG3-MNs for OC. RG3-MNs may serve as an intelligent drug delivery strategy and a new research direction to provide painless and precise treatment for OC patients. The flow chart of this study is shown in Fig. 1.