Related Experiment Video
Updated: Aug 11, 2026
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
ROS-triggered nanoinducer based on dermatan sulfate enhances immunogenic cell death in melanoma
Qixiong Zhang1, Shanshan Li2, Jiandong Ren1
1Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China.
Abstract:
Due to its complexity, diversity and heterogeneity, melanoma is a kind of malignant tumor. It has been proved that the enhancement of anti-tumor immune response such as immunogenic cell death (ICD) is an important therapeutic strategy. In previous studies, we confirmed that dermatan sulfate (DS) from skin tissue could specifically homing to melanoma B16F10 cells. In this study, we propose a nanoinducer (DOX/ADS NP) based on a functional DS for melanoma. This nanosystem is composed of DS as framework, aromatic thioketal derivative (ATK) as functional grafting unit and doxorubicin (DOX) designed as an ICD inducer. Through the intermolecular interaction between DOX and ATK, DOX/ADS NP with specific-homing, high-loading and ROS-triggering release was obtained via self-assemble. Compared with free DOX and non-functionalized nanomedicine, DOX/ADS NP could release DOX into B16F10 cells better, and strongly induce the translocation of calreticulin (CRT) to the cell membrane. CRT is a marker of ICD, also as a "eat me" signal to stimulate the maturation and antigen presentation of dendritic cells. Therefore, a series of subsequent immune responses were activated: maturation of dendritic cells, T cells proliferation, increased tumor-infiltrating CTLs and the ratio of CTLs to Tregs, and up-regulated cytotoxic cytokine expression. In conclusion, DOX/ADS NP promoted ICD-associated immune response through more specific targeting effect and sensitive responsive DOX release, achieving better inhibitory effect on melanoma than free DOX and other nanoformulation. This biomimetic ICD nanoinducer based on DS is expected to provide new strategies and references for the treatment of melanoma.
Insights
A novel nanomedicine, DOX/ADS NP, effectively targets melanoma cells by inducing immunogenic cell death (ICD). This targeted approach enhances anti-tumor immunity, offering a promising new strategy for melanoma treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Immunology
Background:
- Melanoma is a complex and heterogeneous malignant tumor.
- Enhancing anti-tumor immune responses, particularly immunogenic cell death (ICD), is a key therapeutic strategy.
- Dermatan sulfate (DS) has shown specific homing capabilities to melanoma cells.
Purpose of the Study:
- To develop a functional dermatan sulfate (DS)-based nanoinducer (DOX/ADS NP) for targeted melanoma treatment.
- To investigate the efficacy of DOX/ADS NP in inducing ICD and subsequent anti-tumor immune responses.
Main Methods:
- Self-assembly of DOX/ADS NP using DS as a framework and aromatic thioketal derivative (ATK) for doxorubicin (DOX) loading.
- Evaluation of DOX release triggered by reactive oxygen species (ROS).
- Assessment of ICD induction markers (e.g., calreticulin translocation) and immune cell responses (dendritic cell maturation, T cell proliferation, CTLs, Tregs).
Main Results:
- DOX/ADS NP demonstrated specific targeting and efficient intracellular DOX release in B16F10 melanoma cells.
- The nanosystem effectively induced calreticulin (CRT) translocation, a marker of ICD.
- DOX/ADS NP significantly enhanced anti-tumor immunity, including dendritic cell maturation, T cell proliferation, and increased cytotoxic T lymphocyte (CTL) activity.
Conclusions:
- The biomimetic DOX/ADS NP effectively promotes ICD-associated immune responses through targeted delivery and responsive drug release.
- This nanoinducer achieved superior melanoma inhibition compared to free DOX and other nanoformulations.
- DS-based nanoinducers offer a novel and effective strategy for melanoma treatment by leveraging ICD and immune modulation.
Related Concept Videos
01:30Skin Cancer
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
01:27Tumor Immunotherapy