Self‐Powered Intracellular Drug Delivery by a Biomechanical Energy‐Driven Triboelectric Nanogenerator

Nondestructive, high‐efficiency, and on‐demand intracellular drug/biomacromolecule delivery for therapeutic purposes remains a great challenge. Herein, a biomechanical‐energy‐powered triboelectric nanogenerator (TENG)‐driven electroporation system is developed for intracellular drug delivery with high efficiency and minimal cell damage in vitro and in vivo. In the integrated system, a self‐powered TENG as a stable voltage pulse source triggers the increase of plasma membrane potential and membrane permeability. Cooperatively, the silicon nanoneedle‐array electrode minimizes cellular damage during electroporation via enhancing the localized electrical field at the nanoneedle–cell interface and also decreases plasma membrane fluidity for the enhancement of molecular influx. The integrated system achieves efficient delivery of exogenous materials (small molecules, macromolecules, and siRNA) into different types of cells, including hard‐to‐transfect primary cells, with delivery efficiency up to 90% and cell viability over 94%. Through simple finger friction or hand slapping of the wearable TENGs, it successfully realizes a transdermal biomolecule delivery with an over threefold depth enhancement in mice. This integrated and self‐powered system for active electroporation drug delivery shows great prospect for self‐tuning drug delivery and wearable medicine.

[1]  W. J. Dower,et al.  High efficiency transformation of E. coli by high voltage electroporation , 1988, Nucleic Acids Res..

[2]  R. Langer,et al.  Drug delivery and targeting. , 1998, Nature.

[3]  M J Jaroszeski,et al.  Theory and in vivo application of electroporative gene delivery. , 2000, Molecular therapy : the journal of the American Society of Gene Therapy.

[4]  W. Mark Saltzman,et al.  Enhancement of transfection by physical concentration of DNA at the cell surface , 2000, Nature Biotechnology.

[5]  J. Gehl,et al.  Electroporation: theory and methods, perspectives for drug delivery, gene therapy and research. , 2003, Acta physiologica Scandinavica.

[6]  M. Manoharan,et al.  RNAi therapeutics: a potential new class of pharmaceutical drugs , 2006, Nature chemical biology.

[7]  M. Kiebler,et al.  High-efficiency transfection of mammalian neurons via nucleofection , 2007, Nature Protocols.

[8]  Daniel M. Hallow,et al.  Shear‐induced intracellular loading of cells with molecules by controlled microfluidics , 2008, Biotechnology and bioengineering.

[9]  Zhong Lin Wang,et al.  Quantifying the traction force of a single cell by aligned silicon nanowire array. , 2009, Nano letters.

[10]  Siewert J Marrink,et al.  Lipids on the move: simulations of membrane pores, domains, stalks and curves. , 2009, Biochimica et biophysica acta.

[11]  Jacob T. Robinson,et al.  Vertical silicon nanowires as a universal platform for delivering biomolecules into living cells , 2010, Proceedings of the National Academy of Sciences.

[12]  Yang Guo,et al.  Irreversible electroporation therapy in the liver: longitudinal efficacy studies in a rat model of hepatocellular carcinoma. , 2010, Cancer research.

[13]  J. Lemasters,et al.  Free tubulin modulates mitochondrial membrane potential in cancer cells. , 2010, Cancer research.

[14]  Wei Wang,et al.  An efficient and high-throughput electroporation microchip applicable for siRNA delivery. , 2011, Lab on a chip.

[15]  Jacob T. Robinson,et al.  Vertical nanowire electrode arrays as a scalable platform for intracellular interfacing to neuronal circuits. , 2012, Nature nanotechnology.

[16]  Zhong Lin Wang,et al.  Flexible triboelectric generator , 2012 .

[17]  Yi I. Wu,et al.  External push and internal pull forces recruit curvature sensing N-BAR domain proteins to the plasma membrane , 2012, Nature Cell Biology.

[18]  B. Cui,et al.  Intracellular Recording of Action Potentials by Nanopillar Electroporation , 2012, Nature nanotechnology.

[19]  Yuhong Cao,et al.  Nanostraw-electroporation system for highly efficient intracellular delivery and transfection. , 2013, ACS nano.

[20]  Zhong Lin Wang Triboelectric nanogenerators as new energy technology for self-powered systems and as active mechanical and chemical sensors. , 2013, ACS nano.

[21]  Damijan Miklavčič,et al.  Electroporation-based technologies for medicine: principles, applications, and challenges. , 2014, Annual review of biomedical engineering.

[22]  Ying Wang,et al.  Poking cells for efficient vector-free intracellular delivery , 2014, Nature Communications.

[23]  M. Corrotte,et al.  Damage control: cellular mechanisms of plasma membrane repair. , 2014, Trends in cell biology.

[24]  Chang Bao Han,et al.  Self‐Powered Water Splitting Using Flowing Kinetic Energy , 2015, Advanced materials.

[25]  E. Tasciotti,et al.  Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization. , 2015, Nature materials.

[26]  Kenta Shimizu,et al.  MD simulation study of direct permeation of a nanoparticle across the cell membrane under an external electric field. , 2016, Nanoscale.

[27]  Jungmok Seo,et al.  Triboelectric Nanogenerator Accelerates Highly Efficient Nonviral Direct Conversion and In Vivo Reprogramming of Fibroblasts to Functional Neuronal Cells , 2016, Advanced materials.

[28]  Xiaodi Zhang,et al.  Self-Powered Electrical Stimulation for Enhancing Neural Differentiation of Mesenchymal Stem Cells on Graphene-Poly(3,4-ethylenedioxythiophene) Hybrid Microfibers. , 2016, ACS nano.

[29]  Jung Hyun Lee,et al.  Microscale Symmetrical Electroporator Array as a Versatile Molecular Delivery System , 2017, Scientific Reports.

[30]  Yunlong Zi,et al.  Triboelectric nanogenerators for sensitive nano-coulomb molecular mass spectrometry. , 2017, Nature nanotechnology.

[31]  Ciro Chiappini,et al.  Nanoneedle-Based Sensing in Biological Systems. , 2017, ACS sensors.

[32]  F. Tantussi,et al.  Soft electroporation for delivering molecules into tightly adherent mammalian cells through 3D hollow nanoelectrodes , 2017, Scientific Reports.

[33]  Peiyi Song,et al.  A Self‐Powered Implantable Drug‐Delivery System Using Biokinetic Energy , 2017, Advanced materials.

[34]  Zhong Lin Wang,et al.  A self-powered sterilization system with both instant and sustainable anti-bacterial ability , 2017 .

[35]  I. Whiteley,et al.  Architecture of a mammalian glomerular domain revealed by novel volume electroporation using nanoengineered microelectrodes , 2018, Nature Communications.

[36]  Il-Joo Cho,et al.  MEMS devices for drug delivery☆ , 2017, Advanced drug delivery reviews.

[37]  P. Qiu,et al.  Microfluidic generation of transient cell volume exchange for convectively driven intracellular delivery of large macromolecules. , 2018, Materials today.

[38]  Yubo Fan,et al.  Implantable Energy‐Harvesting Devices , 2018, Advanced materials.

[39]  Beena Rai,et al.  Electroporation of Skin Stratum Corneum Lipid Bilayer and Molecular Mechanism of Drug Transport: A Molecular Dynamics Study. , 2018, Langmuir : the ACS journal of surfaces and colloids.

[40]  Sung Ha Park,et al.  Microneedles integrated with a triboelectric nanogenerator: an electrically active drug delivery system. , 2018, Nanoscale.

[41]  Antoine M. van Oijen,et al.  Steric exclusion and protein conformation determine the localization of plasma membrane transporters , 2018, Nature Communications.

[42]  Lixin Bai,et al.  Metal–Organic‐Framework‐Derived Carbon Nanostructure Augmented Sonodynamic Cancer Therapy , 2018, Advanced materials.