Nanorobots mediated drug delivery for brain cancer active targeting and controllable therapeutics

Abstract

Brain cancer pose significant life-threats by destructively invading normal brain tissues, causing dysneuria, disability and death, and its therapeutics is limited by underdosage and toxicity lying in conventional drug delivery that relied on passive delivery. The application of nanorobots-based drug delivery systems is an emerging field that holds great potential for brain cancer active targeting and controllable treatment. The ability of nanorobots to encapsulate, transport, and supply therapies directly to the lesion site through blood-brain barriers makes it possible to deliver drugs to hard-to-reach areas. In order to improve the efficiency of drug delivery and problems such as precision and sustained release, nanorobots are effectively realized by converting other forms of energy into propulsion and motion, which are considered as high-efficiency methods for drug delivery. In this article, we described recent advances in the treatment of brain cancer with nanorobots mainly from three aspects: firstly, the development history and characteristics of nanorobots are reviewed; secondly, recent research progress of nanorobots in brain cancer is comprehensively investigated, like the driving mode and mechanism of nanorobots are described; thirdly, the potential translation of nanorobotics for brain diseases is discussed and the challenges and opportunities for future research are outlined.

Keywords: Active targeting; Brain cancer; Controllable therapeutics; Precise oncology; Targeted drug delivery nanorobots.

Fig. 1

Schematic illustration of nanorobots mediated drug delivery for brain cancer active targeting and controllable therapeutics

Fig. 2

The development of brain-targeted drug delivery nanorobots

Fig. 3

All kinds of nanorobots developed based on different materials and driving mode. A Carbon nanotube-polymer hybrid nanomaterials as biomacromolecules for anticancer drug delivery systems. Reproduced under the terms of the Creative Commons CC BY license [45]. Copyright © 2024, Informa UK Limited. B Aggregation, dispersion and isolation of nanorobots in a grid of cells in the spinal cortex (black for nanorobots, blue for cancer cells).Reproduced with permission from ref [36]. Copyright © 2014, Institute for Computer Sciences, Social Informatics and Telecommunications Engineering. C Eight-week intensive rehabilitation, including robotic and manual gait training, was well tolerated by patients with early stroke and was associated with significant increases in function. Patients with moderate gait dysfunction showed the strongest improvement after robot training. Reproduced under the terms of the Creative Commons CC BY license [46].Copyright © 2012, Conesa et al.; licensee BioMed Central Ltd. D A simplified representation of the vascular network that must pass through to reach the tumor under closed loop navigation control. Reproduced with permission from ref [27]. Copyright ©Rights managed by AIP Publishing. E The local neuronal population 1 is activated rhythmically, and the resonant response between the synchronous periodic ripple cell populations is observed within the neurons without the need for direct synaptic contact. Reproduced with permission from ref [43]. Copyright © 2023, American Chemical Society. F Schematic diagram of a robotic system for intracranial cross-scale targeted drug delivery. Reproduced with permission from ref [47]. Copyright © 2023, Wiley‐VCH GmbH

Fig. 4

Various shapes of different types of nanorobots. A Needle type. Adapted with permission. [48] Copyright 2020 WILEY‐VCH Verlag GmbH. B Screw-type. Adapted with permission. [49] Copyright 2015 WILEY‐VCH Verlag GmbH. C Bracket type. Adapted with permission. [50] Copyright 2013 WILEY‐VCH Verlag GmbH. D Ciliary type. Reproduced under the terms of the Creative Commons CC BY license. [51] Copyright 2020, the Authors, published by Scientific Reports. E Capsule type. Adapted with permission [52].Copyright 2020 WILEY‐VCH Verlag GmbH. F Nickel-based spherical Janus. Reproduced under the terms of the CC BY-NC 4.0 license. [53] Copyright 2022, the Authors, published by SCIENCE ADVANCES

Fig. 5

Schematic illustration of gold nanoplatform drug delivery across the blood–brain barrier

Fig. 6

A (i) the challenge of treating brain cancer. Reproduced with permission from ref [117]. Copyright © 2024Informa UK Limited. (ii) Genetically engineered NSCs membrane coated nanoformulations and their application in drug delivery in the central nervous system. Reproduced with permission from ref [118]. Copyright © 2023, American Chemical Society. (iii)Load TEM images of Rhodamine's optimized SLN formulation. Reproduced with permission from ref [119]. Copyright © 2024Informa UK Limited. (iv) Release CBD NPs in vitro in the rat brain. Reproduced with permission from ref [120]. © 2022 Elsevier B.V. All rights reserved. Mechanism of drug delivery by different nanocarriers B (i) Effective delivery of adriamycin to PLGA structures in human glioma cells. Reproduced with permission from ref. [90] Copyright 2017 Elsevier B.V. All rights reserved. (ii) Different route schemes for nanobots to administer drugs from the nose to the brain in mice. Reproduced with permission from ref [121]. © 2019 Elsevier B.V. All rights reserved. (iii) Schematic diagram of the therapeutic and diagnostic efficacy of Au NP-mediated brain tumors. Reproduced with permission from ref. [96] Copyright 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. (iv) Silicon dioxide nanoparticles carry RSV across BBB release schematic. (MSNPS are recognized and internalized by the LDL receptors of RBEC, and PMA or LPS stimulate and activate the inflammatory response of microglia, releasing reactive substances). Reproduced with permission from ref [122]. Copyright 2018, the Authors, published by Journal of Nanobiotechnology. (v)An experiment of targeted cancer cell therapy using magnetoactuated three-bead/azo /DOX nanorobots. Reproduced under the terms of the CC BY-NC 4.0 license [123]. Copyright 2021, the Authors, published by Scientific Reports (Sci Rep). (vi) Schematic illustration of ultrasound-driven motion of a nanoporous Au nanomotor loaded with drugs and triggering drug release around cancer cells. Reproduced with permission from ref [124]. © 2014 WILEY–VCH Verlag GmbH. (vii) A schematic showing the translocation of Dox and ERLO-loaded Tf-Pen liposomes across BBB and then endocytosis into glioblastoma tumor cells. Reproduced with permission from ref [125]. © 2019 Elsevier B.V. All rights reserved

Fig. 7

Biological and chemically-driven nanorobots for brain diseases. A NK cells simulate the preparation and assembly process of AIE nanoparticles and NK@AIEdots "smart" modulated TJ penetration of the BBB for brain tumor targeted lighting and inhibition. Reproduced with permission from ref. [9] Copyright 2020 American Chemical Society. B Immunofluorescence histology of polymerized rat hippocampal sections. Reproduced under the terms of the CC BY-NC 4.0 license [126]. Copyright 2017, the Authors, published by SCIENCE ADVANCES. C Diagram of DNA nanorobot treating mice. Adapted with permission. [120] Copyright 2021 WILEY‐VCH GmbH. D Mechanism of action and structure of HPMs for in vivo treatment of acute ischemic stroke. Adapted with permission. [121] Copyright 2021 WILEY‐VCH GmbH

Fig. 8

Magnetically powered nanorobots for brain cancer. A In vitro magnetic drive of a nanorobot in the brain. Reproduced with permission from ref [123].Copyright 2019, the Authors, published by SCIENCE ROBOTICS. B The capsule-shaped nanorobot releases the lid and tranships the ORN cells to a target point on the rat brain slice. Adapted with permission [52]. Copyright 2020 WILEY‐VCH Verlag GmbH. C Noninvasive photoacoustic tomography (OAT) and OAT imaging of a nanorobot in the cerebral vasculature of a mouse. Reproduced under the terms of the CC BY-NC 4.0 license. [53] Copyright 2022, the Authors, published by SCIENCE ADVANCES. D Intracellular robot delivery to the target brain region through intranasal administration and magnetic guidance. Adapted with permission. [124] Copyright 2021 WILEY‐VCH GmbH. E Magnetic power supply voltage SP@Fe3O4@BaTiO3 micromotion targeting neural stem cells schematic diagram. Reproduced with permission from ref. [125] Copyright 2020 American Chemical Society

Fig. 9

Light-driven and hybrid driven nanorobots for brain diseases. A The growth direction of axons can be changed by changing the position and rotation direction of aragonite particles. Reproduced with permission from ref. [131] Copyright 2011, Springer Nature Limited. B Schematic diagram of in vivo active therapy for dual response neutral robot. Reproduced with permission from ref [132]. Copyright 2021,the Authors,published by SCIENCE ADVANCE. C Intracranial drug delivery in GBM therapy provides a real-time in vivo imaging approach. Reproduced with permission from ref [133]. Copyright © 2023 Wiley‐VCH GmbH