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

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). R

SUBMITTER: Yu Q 

PROVIDER: S-EPMC6376180 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature