Janus rod-like micromotors to promote the tumor accumulation and cell internalization of therapeutic agents

Abstract

The navigation of drug-loaded nanocarriers is confronted with series of physiological and pathological barriers in blood circulation, tissue penetration and cell internalization. In the current study, self-propelled micromotors of fiber rods are proposed to address the transportation barriers of chemotherapeutic drugs. Fiber rods with distinct Janus structure are prepared by side-by-side electrospinning, and urease and folate are conjugated on the respective sides of Janus rods (JRs) as power source and targeting ligands of Janus micromotors (JMs). The grafting density of urease determines the motion velocity and trajectory of JMs, and the high motion velocity and large mean-square displacement are detected in both phosphate-buffered saline and simulated extracellular matrices of tumor tissues. Despite no interference with the uptake pathway, the self-propelled motion promotes the folate-mediated cell internalization of JMs and maximizes the toxicities and apoptosis rate of tumor cells. The self-propulsion force from one side of JMs enhances the lateral drift and extravasation across blood vessel walls, increasing their accumulation in tumor tissues by around 2 folds and, doxorubicin accumulation, by around 2.6 folds. The treatment with JMs remarkably inhibits the tumor growth, prolongs the animal survival rate and induces strong tumor necrosis without obvious histopathological and hematological abnormalities to normal tissues. Thus, this study demonstrates a feasible strategy in combating the navigation barriers of blood vessel extravasation, tumor tissue diffusion and cell capture, effectively promoting the treatment efficacy and alleviating side effects of chemotherapeutic agents.