Precise Control of Customized Macrophage Cell Robot for Targeted Therapy of Solid Tumors with Minimal Invasion

Abstract

stimuli generate driving forces from the interaction between the micro/nanorobots and aspects of the treatment microenvironment, such as pH, enzymes, and redox potential. [4][5][6][7][8][9] However, the controllability of endogenous power-driven cell robots is limited, considering tumor heterogeneity. In addition, the cell robots may lose driving force when local lesions are cured. In contrast, driving forces generated from externally-applied fields are controllable, and can be output continuously. Micro/ nanorobots for biomedical applications, driven by optical, [9][10][11][12][13] acoustic, [14][15][16][17][18] or magnetic fields, [19][20][21][22][23] have been reported. In particular, micro/nanorobots controlled by magnetic fields have been studied extensively, because magnetic fields can penetrate tissues without attenuation of energy. [23][24][25][26] In general, magneticallycontrolled micro/nanorobot systems can be divided into two components: the magnetic manipulation platform (MMP), and the magnetized micro/nanorobot (MMR). The MMP relies primarily on the characteristics of superimposed magnetic fields, generated by different coils, that can be oriented in any desired direction. [27,28] To be biocompatible, cell membranes, [29] cell derived vesicles, [30] or natural cells [31,32] can be used to camouflage MMRs. [33] Magnetized cell-based robots (MCRs) are particularly effective in targeted treatment of tumors, owing to their homology with the patient, which not only gives the cell carrier excellent biocompatibility, but also takes advantage of the cells' specialized functions. [34,35] MCR fabrication is typically manifested as adhesion of magnetic materials to the cell membrane, or entry of magnetic materials to the cell by means, such as electrostatic adsorption or endocytosis. Examples of the latter strategy include the loading of red blood cells, [36][37][38] macrophages, [32,39] and stem cells [40,41] with iron oxide nanoparticles (NPs) containing drugs, for effective targeting of lesion locations under magnetic drive. However, with this strategy, drug loading is limited, to avoid influencing the activity of cells. An alternative strategy is to wrap the drugs in a membrane, and release them when the cell robots reach the lesion location. For example, liposome or polymer NPs can be loaded into live macrophages thanks to their natural phagocytic function, and the load-drugs can subsequently be released under endogenous or exogenous Injecting micro/nanorobots into the body to kill tumors is one of the ultimate ambitions for medical nanotechnology. However, injecting current micro/ nanorobots based on 3D-printed biocompatible materials directly into blood vessels for targeted therapy is often difficult, and mistakes in targeting can cause serious side effects, such as blood clots, oxidative stress, or inflammation. The natural affinity of macrophages to tumors, and their natural phagocytosis and ability to invade tumors, make them outstanding drug delivery vehicles for targeted tumor therapy. Hence, a mag...

Macrophage Cell Membrane‐Cloaked Nanoplatforms for Biomedical Applications

“…[77] Another example is the encapsulation of magnetic NPs that capable of migrating to tumor sites under external magnetic guidance. [78] The results of these studies demonstrate the potential of living macrophages as cell-based delivery vehicles for targeted and precise cancer therapy.…”

Magnetically Actuated Cell‐Robot System: Precise Control, Manipulation, and Multimode Conversion

“…[40,[49][50][51][52] In a previous experiment, we used macrophages that were loaded with DOX drugs for targeted tumor therapy in vivo, and they were found to have an effective therapeutic effect. [20] Therefore, the targeted precision control of macrophage-based cell robots has promising applications in tumor-targeted therapy. [40,53] Additionally, the control flexibility characteristic of cell robots makes it possible to conduct micromanipulation using the flow field around the moving cell robot, including the transportation of various micro-objects such as cells.…”

“…By providing these biological robots with new characteristics, they can be propelled by an external field to achieve various functions. For example, researchers have created cell-based delivery systems with the property of low toxicity and immunogenicity including the red blood cells, [17] platelets, [18] stem cells, [19] immune cells, [20] and tumor cells [21] that could be controlled to achieve precise site-specific delivery with better treatment efficacy. [22,23] Recently, magnetically propelled microrobots have gained particular attention in the bioengineering field, since magnetic fields are capable of penetrating most materials with minimal interaction and are nearly harmless.…”

Parallel Manipulation and Flexible Assembly of Micro-Spiral via Optoelectronic Tweezers

“…Optoelectronic tweezers, different from conventional non-contact micro-/nanomanipulation technology [e.g., magnetic control ( Lin et al, 2016 ; Dai et al, 2021 ), ultrasonic manipulation ( Zhang W. et al, 2021 ), dielectrophoresis ( Collet et al, 2015 ), and optical tweezers ( Cheah et al, 2014 )], utilize visual patterns to form virtual optical electrodes in a photoelectric layer. Then, it can generate a non-uniform electric field to achieve parallel independent manipulation of particles ( Chiou et al, 2005 ), and adjusting the visual patterns can flexibly manipulate a large number of micro-/nano-objects ( Liang et al, 2020 ; Puerto et al, 2020 ; Chu et al, 2021 ), such as cells ( Yang et al, 2010 ; Chu et al, 2020 ), microorganisms ( Mishra et al, 2016 ), and gold nanoparticles ( Jamshidi et al, 2009 ).…”