Magnetic propelled hydrogel microrobots for actively enhancing the efficiency of lycorine hydrochloride to suppress colorectal cancer

Abstract

Research and development in the field of micro/nano-robots have made significant progress in the past, especially in the field of clinical medicine, where further research may lead to many revolutionary achievements. Through the research and experiment of microrobots, a controllable drug delivery system will be realized, which will solve many problems in drug treatment. In this work, we design and study the ability of magnetic-driven hydrogel microrobots to carry Lycorine hydrochloride (LH) to inhibit colorectal cancer (CRC) cells. We have successfully designed a magnetic field driven, biocompatible drug carrying hydrogel microsphere robot with Fe₃O₄ particles inside, which can achieve magnetic field response, and confirmed that it can transport drug through fluorescence microscope. We have successfully demonstrated the motion mode of hydrogel microrobots driven by a rotating external magnetic field. This driving method allows the microrobots to move in a precise and controllable manner, providing tremendous potential for their use in various applications. Finally, we selected drug LH and loaded it into the hydrogel microrobot for a series of experiments. LH significantly inhibited CRC cells proliferation in a dose- and time-dependent manner. LH inhibited the proliferation, mobility of CRC cells and induced apoptosis. This delivery system can significantly improve the therapeutic effect of drugs on tumors.

Keywords: Fe3O4 particle; colorectal cancer; lycorine hydrochloride; magnetic-driven; microrobots.

FIGURE 1

Targeted drug release in intestine using magnetic-driven hydrogel microrobots. (A) Schematic overview of magnetic-driven hydrogel microrobots for drug release in intestine. (B) The fabrication of magnetic-driven hydrogel microrobots using microfluidic chip. (C) The optical microscopy image of magnetic-driven hydrogel microrobots. (D) Fluorescence microscopic images of magnetic-driven hydrogel microrobots. (E) Particle size distribution of magnetic-driven hydrogel microrobots.

FIGURE 2

Magnetically actuated motility of magnetic-driven hydrogel microrobots. (A)Tracking lines illustrating the traveled distances of microrobots of different sizes over a 14 s period in a rotating uniform magnetic field of 15 mT and 5 Hz. (B) The velocity of microrobots of different sizes varied with the drive frequency from 2 to 40 Hz.

FIGURE 3

Controllable and flexible motility performance of magnetic-driven hydrogel microrobots. (A) Change of the direction of movement of the microrobots caused by changing the magnetic field. (B) Controllable motion of microdimer swimmer.

FIGURE 4

Effect of LH and LH-robot on CRC cell proliferation. (A) Chemical and three-dimensional structures of LH. (B) An MTT assay was performed to measure CRC cell viability following LH (0–100 µM) treatment. (C) The influence of LH alone and LH-robot on the colony formation of CRC cells. *p < 0.05 and **p < 0.01 and ***p < 0.001 vs. NC group.

FIGURE 5

Effect of LH and LH-robot on CRC cell mobility. (A) Wound healing assay of LH alone and LH-robot on CRC cells at non-toxic concentrations (20µM, 24 h). Magnification, ×100. (B) Invasion assays of CRC cells pretreated with LH and LH-robot at non-toxic concentrations (20µM, 24 h). Magnification, ×100. *p < 0.05 and **p < 0.01 and ***p < 0.001 vs. NC group.

FIGURE 6

The apoptosis of CRC cells after treatment of LH and LH-robot separately. *p < 0.01 and ***p < 0.001 vs. NC group.