Feasibility study of using macrophages as drug delivery carriers for drug-loaded phase-change droplets

Tumors normally possess irregular vasculature, and tend to outstrip blood supplement and become hypoxia or ischemia, resulting in the resistances of the tumor to conventional chemotherapy and radiotherapy. New therapies are required to target hypoxic or ischemic areas in tumors. In this study, we investigate the feasibility of using macrophages to infiltrate hypoxic or ischemic areas in tumors, as the carriers of drug-loaded phase-change droplets. RAW 264.7 cells (mouse leukaemic monocyte macrophage cell line) were used to ingest the drug-loaded phase-change droplets. The droplets were composed of lipid, perfluoropentane (PFP) and chemotherapeutic drug - doxorubicin (DOX). Fluorescence spectrophotometer was used to quantify the drug encapsulation efficiency. For evaluating DOX-droplets uptake efficiency, cell viability and migration mobility of DOX-droplet loaded macrophages, flow cytometric analysis, Alamar Blue assay, and transmembrane cell migration assay were measured, respectively. The results demonstrate the feasibility of using macrophages to deliver DOX-loaded phase-change droplets. Ultrasound-triggered vaporization was also performed to investigate the drug liberation efficiency from the droplet-loaded macrophages. Future works include the assessments of the tumor infiltration ability of droplet-loaded macrophages and the liberated drug payload via ultrasound-triggered vaporization in vivo.