Magnetically and Near‐Infrared Light‐Powered Supramolecular Nanotransporters for the Remote Control of Enzymatic Reactions

Abstract

Cancer is one of the primary causes of death worldwide.Ahigh-precision analysis of biomolecular behaviors in cancer cells at the single-cell level and more effective cancer therapies are urgently required. Here,w ed escribe the development of am agnetically-and near infrared lighttriggered optical control method, based on nanorobotics,f or the analyses of cellular functions.An ew type of nanotransporters,c omposed of magnetic iron nanoparticles,c arbon nanohorns,a nd liposomes,w as synthesized for the spatiotemporal control of cellular functions in cells and mice.O ur technology will help to create anew state-of-the-art tool for the comprehensive analysis of "real" biological molecular information at the single-cell level, and it maya lso help in the development of innovative cancer therapies.Cancer development starts from one single cell that changes its normal behavior and fate.[1] This transformation from normal to tumor cell is am ultistage process,t ypically representing ap rogression from ap re-cancerous lesion to malignant tumor.T hese changes are the result of the interactions between individual genetic factors and external agents.O ver the last decades,t he analyses of cancer risk factors and the early detection strategies have been developing rapidly.[2] However,ahigh-precision analysis of the biomolecular behaviors of cancer cells at the single-cell level has not been investigated thoroughly,a nd efficient therapies are not available yet. Additionally,d ata demonstrating how anticancer drugs affect asingle cancer cell have not been explored. Thei nformation about tumor microenvironment, and the development of the strategies for cancer prevention and management could be valuable in avariety of cancer treatments.W ebelieve that many types of cancer can be reduced and controlled by implementing strategies for single-cell manipulation and external control or by as trict control of molecular behaviors in cancer cells.Theemerging field of nanorobotics [3] has the objective to associate different classes of molecules with av ariety of materials,i no rder to obtain new functionalities.T his approach also allows the development of advanced and performing devices endowed of multifunctional modalities in different fields of applications,i ncluding biomedicine and nanomedicine.I nt he past decades,t he continuous development of nanotechnology has brought innovations in biomedicine,l eading to remarkable improvements in the fields of therapy,imaging,and diagnosis. [4][5][6] Thecontrolled delivery of bioactive agents and the local treatment of diseases represent an ovel perspective in the development of efficient multifunctional therapeutics.[7] Thefuture goals of nanorobotics in the fields of biology and biomedicine are those allowing progress in the temporal and spatial site-specific drug delivery,l ocal therapy,i maging,a nd cellular manipulation of biological processes.H owever,t hese studies are still relatively immature.P reviously developed nanocomplexes, such as self-assembled and supramolecular na...

Photothermogenetic inhibition of cancer stemness by near-infrared-light-activatable nanocomplexes

“…Preparation and characterisation of CNH complexes. We selected CNHs as model photo-exothermic nanomaterials due to their strong photothermal conversion effect [17][18][19] and high in vitro and in vivo biocompatibility [22][23][24] . To develop CNHs as photothermogenetic tools for use under physiological conditions, we improved water dispersibility using a PEGylation technique.…”

“…Among NIR regions, the second NIR optical window (NIR-II, 1000-1700 nm) has advantages of deeper tissue penetration and higher maximum permissible light exposure 28 . CNHs have been shown to be capable of absorbing light in NIR-II region [17][18][19] . We anticipated that the utilisation of NIR-II lightinduced CNHs will lead to promising applications in treating deep-tissue-cancer.…”

“…Cho et al achieved remote control of apoptosis by manipulating magnetic nanoparticles with a targeting antibody for death receptor 4 in colon cancer cells 14 . To overcome the challenges of clinical application by regulating cellular activities, we developed biopermeable near-infrared (NIR) light-driven exothermic nanomaterials, including carbon nanotubes (CNTs) 15,16 , carbon nanohorn (CNH) [17][18][19] , liquid metal nanocomplexes 20 , and semiconducting polymer nanoparticles 21 . In these studies, we demonstrated the use of these nanomaterials for photo-thermally controlling heat-sensitive TRPV1 or TRPV2 ion channels on cell membrane to stimulate cells that we call "photothermogenetics".…”

Stimulus-responsive liposomes as smart nanoplatforms for drug delivery applications

“…Simultaneous magnetic field and laser induction were used to trap the nanotranporters in the vessels of the mouse ear, and release the FDG. Due to β-Gal enzymatic reaction, the green fluorescence of fluorescein was produced by hydrolysis of FDG and could be directly observed in vivo [190].…”

“…d) Nanotransporter structure Reprinted with permission from ref. [190], copyright 2016, John Wiley & Sons, Inc.…”