Novel Therapeutic Approach Using Drug-loaded Adipose-derived Stem Cells for Pancreatic Cancer

Abstract

We developed anticancer drug-conjugated biodegradable polymer-nanoparticle-loaded adipose-derived stem cells (AdSCs) as a tool for biodrug delivery systems for cancer therapy. Pirarubicin was conjugated in polylactic/glycolic acid (PLGA) followed by formation of nanoparticles (NPs), which were loaded with human AdSCs and cocultured. The pirarubicin-conjugated PLGA NP-loaded AdSCs (PirNP-AdSCs) were overall viable within 48 h and exhibited significantly enhanced migration activity. We confirmed that pirarubicin was gradually released into the culture medium from PirNP-AdSCs, and the conditioned medium significantly inhibited the proliferation activity and induced the apoptosis of human pancreatic cancer cells (KP1N). PirNP-AdSCs also significantly induced tumor cell apoptosis in an ex vivo culture system with KP1N-derived tumors, and there was increased invasion/migration of PirNP-AdSCs inside the tumor. Finally, we compared the therapeutic efficacy of the PirNP-AdSCs on KP1N-derived tumor growth with that of treatments of AdSCs alone, PirNPs alone or normal saline (control) in immunodeficient mice. Subcutaneous local administration of PirNP-AdSCs significantly inhibited tumor growth, inducing the apoptosis of tumor cells and vasculature compared with the other groups. The present therapeutic strategy might give rise to a novel cancer therapy minimizing the adverse side effects of anticancer drugs in patients who suffer from cancer.