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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
A pH-triggered N-oxide polyzwitterionic nano-drug loaded system for the anti-tumor immunity activation research
Yan Zhao1, Yuansong Bai2, Mei Li1
1Department of Medical Oncology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, China.
Abstract:
Triple negative breast cancer (TNBC) has the characteristics of low immune cell infiltration, high expression of tumor programmed death ligand 1 (PD-L1), and abundant cancer stem cells. Systemic toxicity of traditional chemotherapy drugs due to poor drug selectivity, and chemotherapy failure due to tumor drug resistance and other problems, so it is particularly important to find new cancer treatment strategies for TNBC with limited treatment options. Both the anti-tumor natural drugs curcumin and ginsenoside Rg3 can exert anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells, reducing PD-L1 expression, and reducing cancer stem cells. However, they have the disadvantages of poor water solubility, low bioavailability, and weak anti-tumor effect of single agents. We used vinyl ether bonds to link curcumin (Cur) with N-O type zwitterionic polymers and at the same time encapsulated ginsenoside Rg3 to obtain hyperbranched zwitterionic drug-loaded micelles OPDEA-PGED-5HA@Cur@Rg3 (PPH@CR) with pH response. In vitro cell experiments and in vivo animal experiments have proved that PPH@CR could not only promote the maturation of dendritic cells (DCs) and increase the CD4+ T cells and CD8+ T cells by inducing ICD in tumor cells but also reduce the expression of PD-L1 in tumor tissues, and reduce cancer stem cells and showed better anti-tumor effects and good biological safety compared with free double drugs, which is a promising cancer treatment strategy.
Insights
A novel drug delivery system, PPH@CR, combines curcumin and ginsenoside Rg3 to treat triple-negative breast cancer (TNBC). This system enhances anti-tumor immunity, reduces PD-L1 expression, and targets cancer stem cells, offering a promising new strategy.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Immunotherapy
Background:
- Triple-negative breast cancer (TNBC) presents challenges due to low immune infiltration, high PD-L1 expression, and abundant cancer stem cells.
- Conventional chemotherapy for TNBC faces limitations including systemic toxicity, drug resistance, and limited treatment options.
- Curcumin and ginsenoside Rg3 show anti-tumor potential by inducing immunogenic cell death (ICD), reducing PD-L1, and decreasing cancer stem cells, but suffer from poor solubility and bioavailability.
Purpose of the Study:
- To develop a novel drug delivery system for co-delivering curcumin and ginsenoside Rg3 for enhanced TNBC treatment.
- To investigate the efficacy of the developed system in modulating the tumor immune microenvironment and targeting cancer stem cells.
- To evaluate the anti-tumor effects and biological safety of the novel drug delivery system.
Main Methods:
- Synthesis of pH-responsive hyperbranched zwitterionic micelles (PPH@CR) encapsulating curcumin (Cur) and ginsenoside Rg3 (Rg3) using vinyl ether bonds.
- In vitro cell experiments to assess immunogenic cell death (ICD) induction, dendritic cell (DC) maturation, and T cell responses.
- In vivo animal studies to evaluate anti-tumor efficacy, PD-L1 expression, cancer stem cell reduction, and overall biological safety.
Main Results:
- PPH@CR successfully co-delivers curcumin and ginsenoside Rg3, demonstrating pH responsiveness.
- The system effectively induces ICD in tumor cells, promoting DC maturation and increasing CD4+ and CD8+ T cell populations.
- PPH@CR significantly reduces PD-L1 expression in tumor tissues, decreases cancer stem cells, and exhibits superior anti-tumor effects and safety compared to free drugs.
Conclusions:
- The developed PPH@CR micelle system is a promising strategy for treating triple-negative breast cancer.
- This approach enhances anti-tumor immunity and overcomes limitations of individual drugs, offering a potentially effective and safer therapeutic option.
- Further research into this novel drug delivery system could lead to improved clinical outcomes for TNBC patients.
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