Chemotherapy priming of the Pancreatic Tumor Microenvironment Promotes Delivery and Anti-Metastasis Efficacy of Intravenous Low-Molecular-Weight Heparin-Coated Lipid-siRNA Complex
| Autor: | Ling Mei, Man Li, Qin He, Xuhui Wang, Haiyao Wu, Yue Qiu, Yayuan Liu, Qianwen Yu, Zhirong Zhang, Kai Liu, Xiaoxiao Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
tumor priming
medicine.medical_treatment pancreatic cancer Medicine (miscellaneous) 02 engineering and technology Metastasis Extracellular matrix chemistry.chemical_compound Mice Pancreatic tumor Tumor Microenvironment RNA Small Interfering low-molecular-weight heparin Pharmacology Toxicology and Pharmaceutics (miscellaneous) 0303 health sciences Drug Carriers 021001 nanoscience & nanotechnology Treatment Outcome Paclitaxel Drug delivery 0210 nano-technology Research Paper Cell Survival Cytological Techniques Transplantation Heterologous Antineoplastic Agents Adenocarcinoma 03 medical and health sciences Drug Therapy In vivo Pancreatic cancer Cell Line Tumor medicine chemo-gene therapy metastasis Animals Humans 030304 developmental biology Chemotherapy business.industry Heparin Low-Molecular-Weight Models Theoretical medicine.disease Pancreatic Neoplasms Disease Models Animal chemistry Liposomes Cancer research business Neoplasm Transplantation |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| Popis: | Pancreatic ductal adenocarcinoma (PDAC) is a type of malignant tumor with high lethality. Its high tumor cell-density and large variety of extracellular matrix (ECM) components present major barriers for drug delivery. Methods: Paclitaxel-loaded PEGylated liposomes (PTX-Lip) were used as a tumor-priming agent to induce tumor cell apoptosis and decrease the abundance of ECM to promote cellular uptake and tumor delivery of nanodrugs. Paclitaxel exerts anti-cancer effects but, paradoxically, exacerbates cancer metastasis and drug resistance by increasing the expression of apoptotic B-cell lymphoma-2 protein (BCL-2). Thus, low-molecular-weight heparin-coated lipid-siRNA complex (LH-Lip/siBCL-2) was constructed to inhibit cancer metastasis and silence BCL-2 by BCL-2 siRNA (siBCL-2). Results: Significant tumor growth inhibition efficacy was observed, accompanied by obvious inhibition of cancer metastasis in vivo. Conclusion: These results suggested our sequential delivery of PTX-Lip and LH-Lip/siBCL-2 might provide a practical approach for PDAC or other ECM-rich tumors. |
| Databáze: | OpenAIRE |
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