Nanocomposite cascading sequential treatment hydrogel patch for postoperative tumor elimination, immune regulation and tissue regeneration after melanoma surgery
image: In this study, a nanocomposite hydrogel wound patch (MxNd/yCe@M SAC) with cascade sequential therapy was developed, aiming at promoting tissue repair through tumor targeted therapy-immune environment regulation sequential therapy.
Credit: Nano Research, Tsinghua University Press
An ideal postoperative treatment for malignant melanoma should not only focus on eliminating residual tumors but also pay attention to the regeneration of skin tissue. However, it is challenging to manage these two processes in a coordinated manner, as the management procedures for healthy cells and tumor cells overlap yet require opposing approaches. Acral lentiginous melanoma (ALM), one of the common subtypes of melanoma, has an extremely high incidence rate. It mainly occurs on the fingers and soles of the feet—areas that are difficult to treat. This difficulty arises because bulky dressings offer poor comfort and are prone to displacement during strenuous joint movements.
The team of Daidi Fan and Junfeng Hui from the School of Chemical Engineering, Northwest University recently demonstrated a nanocomposite hydrogel wound patch (MxNd/yCe@M SAC) for cascaded sequential therapy. This patch enables sequential therapy involving tumor-targeted treatment and immune microenvironment regulation, thereby promoting tissue repair.
Methotrexate (MTX) was anchored to bioactive glass doped with dual ions (Nd and Ce), and the composite was then encapsulated in a hydrogel composed of sulfobetaine-polyacrylamide-carboxylated chitosan to fabricate the hydrogel wound patch. The resulting MxNd/yCe@M SAC exhibits strong adhesiveness, allowing it to adhere to facial and joint areas in the form of a thin film while adapting to joint movements. Additionally, the obtained MxNd/yCe@M SAC demonstrates the property of self-switching between therapeutic modules, triggered by the pathological microenvironment.
The team published their research article in Nano Research on November 29, 2025.
The research team reported that after melanoma resection, MxNd/yCe@M SAC demonstrated sequential therapeutic characteristics driven by the pathological microenvironment. In the early postoperative stage, the acidic tumor microenvironment induced by residual cancer cells triggered the disintegration of the hydrogel matrix via amide bond activation, releasing MTX-loaded nanoparticles that targeted tumor cells. Here, MTX combined with mild photothermal therapy (mPTT) to achieve synergistic cancer cell ablation. As the treatment progressed to the mid-stage, sustained MTX release continued eliminating residual tumors while simultaneously reducing inflammation by downregulating pro-inflammatory cytokines. In the final repair phase, degradation of MxNd/yCe@M SAC released bioactive ions (Si⁴⁺, Ca²⁺, P⁵⁺, and Ce³⁺), which promoted angiogenesis and extracellular matrix remodeling to facilitate tissue regeneration. To validate this approach.
First, the researchers improved the nanoparticle formulation, focusing on particle size and metal ion content. This ensures that the nanoparticles can be effectively internalized by tumor cells and exert maximum therapeutic efficacy while minimizing toxic side effects.
To obtain a comfortable dressing suitable for ALM treatment, MxNd/yCe@M was physically encapsulated in a hydrogel composed of sulfobetaine (SBMA), polyacrylamide (AM), and carboxymethyl chitosan (Cycs). A hydrogel wound patch (MxNd/yCe@M GOC) was then prepared via a thermal polymerization process. Leveraging the high dipole moment of SBMA, this wound patch exhibits excellent bioadhesiveness, allowing it to adhere tightly to highly mobile joint areas and conform to joint movements.
The researchers tested the release behavior and endocytosis process of MxNd/yCe@M. In vivo full-thickness skin defect experiments, it was found that MxNd/yCe@M SAC could effectively shorten the inflammatory phase, promote the wound to enter the remodeling phase, and accelerate the wound healing time. In addition, a skin melanoma recurrence model was established, which confirmed that melanoma was almost completely eliminated under the combined action of MTX and photothermal therapy.
Other contributors include Jialing Yao, Qingjie Pei, Yujia Xin, Wenyan Qiao, Jiaxin Yao, Yanyan Xuan, Haohan Guo, Ledan Qi from the School of Chemical Engineering, Northwest University; Shaanxi Key Laboratory of Biomaterials and Synthetic Biology
This work was supported by the National key Research and development program of China (2022YFC2106100), and the National Natural Science Foundation of China (No. 22078265).
About Nano Research
Nano Research is a peer-reviewed, open access, international and interdisciplinary research journal, sponsored by Tsinghua University and the Chinese Chemical Society, published by Tsinghua University Press on the platform SciOpen. It publishes original high-quality research and significant review articles on all aspects of nanoscience and nanotechnology, ranging from basic aspects of the science of nanoscale materials to practical applications of such materials. After 18 years of development, it has become one of the most influential academic journals in the nano field. Nano Research has published more than 1,000 papers every year from 2022, with its cumulative count surpassing 7,000 articles. In 2024 InCites Journal Citation Reports, its 2024 IF is 9.0 (8.7, 5 years), and it continues to be the Q1 area among the four subject classifications. Nano Research Award, established by Nano Research together with TUP and Springer Nature in 2013, and Nano Research Young Innovators (NR45) Awards, established by Nano Research in 2018, have become international academic awards with global influence.