Chemotherapy priming of the Pancreatic Tumor Microenvironment Promotes Delivery and Anti-Metastasis Efficacy of Intravenous Low-Molecular-Weight Heparin-Coated Lipid-siRNA Complex

Theranostics
Qianwen YuQin He

Abstract

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.

Citations

Nov 27, 2019·Cancers·Lucia SalvioniDavide Prosperi
Jan 15, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Jiatao YangZhou Zhou
Jan 10, 2020·Biomaterials·Xuexiang HanGuangjun Nie
Apr 10, 2021·Biomaterials·Yachao ZhangShuangying Gui
Sep 7, 2021·International Journal of Pharmaceutics·Jiatao YangZhou Zhou

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Methods Mentioned

BETA
electrophoresis
flow cytometry
blood
transfection

Software Mentioned

GraphPad
GraphPad Prism

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