Magnetic Biohybrid Microrobot Multimers Based on Chlorella Cells for Enhanced Targeted Drug Delivery

Abstract

Magnetic micro-/nanorobots have been regarded as a promising platform for targeted drug delivery, and tremendous strategies have been developed in recent years. However, realizing precise and efficient drug delivery in vivo still remains challenging, in which the versatile integration of good biocompatibility and reconfiguration is the main obstacle for micro-/nanorobots. Herein, we proposed a novel strategy of magnetic biohybrid microrobot multimers (BMMs) based on Chlorella (Ch.) and demonstrated their great potential for targeted drug delivery. The spherical Ch. cells around 3–5 μm were magnetized with Fe3O4 to fabricate biohybrid microrobots and then loaded with doxorubicin (DOX). Using magnetic dipolar interactions, the microrobot units could reconfigure into chain-like BMMs as tiny dimers, trimers, and so forth via attraction-induced self-assembly and disassemble reversibly via repulsion. The BMMs exhibited diverse swimming modes including rolling and tumbling with high maneuverability, and the rolling dimer’s velocity could reach 107.6 μm/s (∼18 body length/s) under a 70 Gs precessing magnetic field. Furthermore, the BMMs exhibited low cell toxicity, high DOX loading capacity, and pH-triggered drug release, which were verified by chemotherapy experiments toward HeLa cancer cells. Due to the remarkable versatility and facile fabrication, the BMMs demonstrate great potential for targeted anticancer therapy.

Bio-Inspired Micro- and Nanorobotics Driven by Magnetic Field

“…These multifunctional micro- and nanorobots have unique capabilities, including fast movement in complex physiological environments and high transport loads. This allows the use of magnetic micro- and nanoscale biomimetic structures in medicine for the diagnosis and treatment of various diseases, targeted drug delivery within living organisms, and minimally invasive surgery [ 169 , 170 , 171 , 172 , 173 ]. In nature, the limbs of living organisms and the surfaces of many organs and tissues are covered with different ciliated microstructures.…”

Biohybrid Magnetic Microrobots for Tumor Assassination and Active Tissue Regeneration

“…Micro-/nanorobotics have attracted significant interest for diverse biomedical applications, such as active drug delivery, regenerative medicine, biosensing, precise surgery, and detoxification. − Various actuation strategies for controlling micro-/nanorobots were reported, including biological hybrid, − chemical propelling, − and external field (e.g., electric, magnetic, light, and ultrasonic field). − Among them, magnetically controlled actuation has been widely used for its programmability, wireless feature, and penetrating capacity. − Great progress has also been made on the design, fabrication, imaging, and biodegradability of the microrobots, trying to put forward the comprehensive application of microrobots to bedside. − To fabricate the desired microrobots with specific functions, diverse fabrication strategies, including chemical synthesis and physical micromachining, were developed. − For instance, emulsion templating and microfluidics methods have been utilized for the fabrication of medical microrobot. , In order to rationally design and produce microrobots with diverse morphologies at microscale, precision printing technologies like 3D laser lithography and two-photon printing, were developed, and thus microrobots with a variety of morphologies were reported and utilized in biomedical scenes. − However, these fabrication methods were limited by the cost-effectiveness, complexity, and scalability.…”

Multifunctional Yolk–Shell Structured Magnetic Mesoporous Polydopamine/Carbon Microspheres for Photothermal Therapy and Heterogenous Catalysis

“…Magnetic materials possess peculiar chemical and physical properties including magnetocaloric effect, strong magnetic resonance and responsiveness, and so on. As a result, they play the decisive role in magnetically targeted drug delivery, , thermal therapy for cancer, , separation, , sensors, , magnetic resonance imaging, , and catalysis. , In contrast, mesoporous materials with a pore diameter at range of 2–50 nm according to the IUPAC, exhibit high surface area, regular pore structure, and large pore volume, and demonstrate potential applications in macromolecule adsorption, , separation and purification, , catalysis, , sensor, , and drug delivery and release. , The noncovalent interaction such as electrostatic attraction or hydrogen bonding interaction between a soft template and framework oligomers drives the assembly and the construction of mesoporous materials with regulated and uniform pore size, nanostructure, specific composition, and surface property. Integrating the properties of magnetism and mesoporous structure to prepare yolk–shell structure with magnetic core, intermediate void, and mesoporous shell have aroused intriguing attentions owing to internal magnetic core with superparamagnetic and quick magnetic response speed as well as the cavity and mesoporous shell providing more active sites, channels, and space for transportation, storage, and fixation. − …”

“…Magnetic materials possess peculiar chemical and physical properties including magnetocaloric effect, strong magnetic resonance and responsiveness, and so on. As a result, they play the decisive role in magnetically targeted drug delivery, 1,2 thermal therapy for cancer, 3,4 separation, 5,6 sensors, 7,8 magnetic resonance imaging, 9,10 and catalysis. 11,12 In contrast, mesoporous materials with a pore diameter at range of 2−50 nm according to the IUPAC, exhibit high surface area, regular pore structure, and large pore volume, and demonstrate potential applications in macromolecule adsorption, 13,14 separation and purification, 15,16 catalysis, 17,18 sensor, 19,20 and drug delivery and release.…”