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Updated: Jan 28, 2026
Isolated Hepatic Perfusion as a Treatment for Liver Metastases of Uveal Melanoma
Published on: January 25, 2015
Low Molecular Weight Heparin-Coated and Dendrimer-Based Core-Shell Nanoplatform with Enhanced Immune Activation and
Chunyu Xia1, Sheng Yin1, Shanshan Xu1
1Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, China.
Abstract:
High-efficiency treatment for tumor is not easy to achieve owing to the existence of metastasis, which remains the arch-criminal of most tumor deaths. Conventional chemotherapy exhibits insufficient inhibitory efficiency on tumor metastasis and more powerful strategies to conquer metastatic tumors are urgently needed. In this study, a rational chemoimmunotherapy strategy was adopted to treat highly aggressive melanoma based on a newly developed multifunctional nanoplatform. Firstly, immunoadjuvant cytosine-phosphate-guanine oligonucleotides (CpG ODNs) were used to boost the doxorubicin (DOX)-elicited immune responses, which synergistically suppressed tumor growth and metastasis. And the anti-metastatic low molecular weight heparin (LMWH) was also integrated, thus multiple anti-metastatic effects to against tumor metastasis were achieved. Methods: G4 PAMAM was serving as the main support to conjugate DOX by pH-sensitive hydrazone bond (PPD) and the synthesized conjugates were confirmed by 1H-NMR spectra, IR spectra and HRMS. Immunoadjuvant CpG ODNs were loaded by electrostatic adsorption to formulate PPD/CpG. After the coating of anti-metastatic LMWH, the designed LMWH/PPD/CpG was fabricated and characterized. The platelets-related and platelets-unrelated anti-metastatic mechanisms were investigated on B16F10 the immune activation effects, anti-tumor and anti-metastatic efficacy of LMWH/PPD/CpG were evaluated on a B16F10 melanoma xenograft model. Results: DOX elicited tumor-specific immune responses by ICD, and the immunological effects could be further promoted by CpG ODNs, exhibiting enhanced maturation of dendritic cells (DCs) and increased level of cytolytic T lymphocytes (CTLs) in vivo. Owing to the coating of LMWH, the platelets-induced epithelial-mesenchymal-like transition of tumor cells was hindered and the actin cytoskeletal arrangement of tumor cells was affected, thus the migration ability of tumor cells was further inhibited. This multifunctional nanoplatform showed enhanced treatment efficiency on melanoma primary tumor and pulmonary metastasis. Conclusion: The immune activation and multiple anti-metastatic effects of LMWH/PPD/CpG establish a novel therapeutic strategy for melanoma. This anti-metastatic nanoplatform could be broadly applied for the co-delivery of other nucleic acids and chemotherapeutic drugs to treat highly aggressive tumors.
Insights
This study presents a novel nanoplatform combining chemotherapy, immunotherapy, and anti-metastatic agents to effectively treat aggressive melanoma. The developed LMWH/PPD/CpG nanoplatform enhances immune responses and inhibits tumor metastasis for improved outcomes.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Research
Background:
- Metastasis is a primary cause of cancer mortality, with conventional chemotherapy showing limited efficacy against it.
- Developing advanced strategies to combat metastatic tumors is crucial for improving patient survival rates.
Purpose of the Study:
- To develop a multifunctional nanoplatform for chemoimmunotherapy to treat aggressive melanoma.
- To enhance anti-tumor and anti-metastatic effects by combining doxorubicin (DOX), cytosine-phosphate-guanine oligonucleotides (CpG ODNs), and low molecular weight heparin (LMWH).
Main Methods:
- A G4 PAMAM-based nanoplatform (PPD) was synthesized, conjugating DOX via a pH-sensitive hydrazone bond.
- Immunoadjuvant CpG ODNs were loaded via electrostatic adsorption, and LMWH was coated to create the LMWH/PPD/CpG nanoplatform.
- The nanoplatform's anti-metastatic mechanisms and therapeutic efficacy were evaluated in vitro and in a B16F10 melanoma xenograft model.
Main Results:
- The nanoplatform elicited tumor-specific immune responses through immunogenic cell death (ICD), enhanced by CpG ODNs, leading to increased dendritic cell maturation and cytolytic T lymphocyte levels.
- LMWH coating inhibited platelet-induced epithelial-mesenchymal-like transition and affected tumor cell actin cytoskeleton, reducing migration.
- The LMWH/PPD/CpG nanoplatform demonstrated enhanced efficacy against primary melanoma tumors and pulmonary metastasis.
Conclusions:
- The developed LMWH/PPD/CpG nanoplatform offers a novel therapeutic strategy for melanoma by combining immune activation and multiple anti-metastatic effects.
- This nanoplatform shows potential for broad application in co-delivering nucleic acids and chemotherapeutics for treating aggressive tumors.
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