A Novel Macrophage-Based Microrobot Bearing Multiple Smart Nanotherapeutics for Targeting and Drug Delivery to Solid Tumors.

In this paper, we propose and evaluate a novel biological macrophage-based microrobot for applications in active targeting and treating of solid tumors. The microrobots are prepared by the phagocytosis of a mouse macrophage cell line with small size gold nanorods (sAuNRs) and anticancer drug (Doxorubicin) contained nanoliposomes (Dox-LPs). First, we synthesize sAuNRs with the average dimensions of 29 nm × 7 nm and high energy absorbance to 808 nm near-infrared (NIR) light. After that we prepare Dox-LPs having an average diameter of 145 nm and thermal sensitive property with over 65% of drug release after 60 min in a 43°C and pH 5.5 condition. After that, we fabricate the microrobots by co-incubation of sAuNRs and Dox-LPs with the macrophages. Experiments with confocal microscopy show that the nanotherapeutics can be readily engulfed by the macrophages. Finally, we evaluate the targeting characteristics of the microrobots to mouse breast cancer (4Tl) cells using a chemotactic test with a 3-D tumor spheroid resembling a solid tumor. Consequently, it is shown that the microrobots can successfully infiltrate into the tumor spheroid. Ultimately, the accompanying sAuNRs can be heated up to trigger the drug liberation from the thermal sensitive liposomes to kill microrobots and the tumor simultaneously.