Efficient co-delivery of doxorubicin and gold nanorod in PLGA nanoparticles coated by TNF-a-treated MSC membrane for cancer treatment

Abstract

Bone marrow-derived mesenchymal stem cells (MSCs) have been extensively studied for cancer therapy using its homing characteristic to injury and tumor tissues. However, MSCs or MSC-derived exosomes would promote tumor growth. To eliminate this risk and take advantage of MSCs, we separated MSC membranes and coated doxorubicin-gold nanorod-PLGA nanoparticles with the membranes (MMNPs). TNF-α-treated MSCs and endothelial cells near tumor shows upregulated vascular cell adhesion molecule-1 (VCAM-1) and very late antigen-4 (VLA-4) on the cell surface. Since VCAM-1 interacts with VLA-4, TNF-α-treated MMNPs (TNF-α MMNPs) exhibited superior tumor vasculature targeting to the polymeric particles or normal MMNPs. Temperature increase by NIR irradiation caused apoptosis of endothelial cells and adjacent cancer cells, and the nanoparticles flowed into deeper cancer cells leading to death of them.