Directing Assembly and Disassembly of 2D MoS2 Nanosheets with DNA for Drug Delivery.

Layer-by-layer (LbL) self-assembled stacked Testudo-like MoS2 superstructures carrying cancer drugs are formed from nanosheets controllably assembled with sequence-based DNA oligonucleotides. These superstructures can disassemble autonomously in response to cancer cells' heightened ATP metabolism. First, we functionalize MoS2 nanosheets (MoS2-NS) nanostructures with DNA oligonucleotides having thiol-terminated groups (DNA/MoS2-NS) via strong binding to sulfur atom defect vacancies on MoS2 surfaces. The driving force to assemble into a higher-order DNA/MoS2-NS superstructure is guided by a linker aptamer that induced interlayer assembly. In the presence of target ATP molecules, these multilayer superstructures disassembled as a consequence of stronger binding of ATP molecules with the linking aptamers. This design plays a dual role of protection and delivery by LbL stacked MoS2-NS similar in concept to a Greek Testudo. These superstructures present a protective armor-like shell of MoS2-NS, which still remains responsive to small and infiltrating ATP molecules diffusing through the protective MoS2-NS, contributing to an enhanced stimuli-responsive drug release system for targeted chemotherapy.

[1]  Weibo Cai,et al.  Iron oxide decorated MoS2 nanosheets with double PEGylation for chelator-free radiolabeling and multimodal imaging guided photothermal therapy. , 2015, ACS nano.

[2]  M. I. Setyawati,et al.  DNA Nanostructures Carrying Stoichiometrically Definable Antibodies. , 2016, Small.

[3]  Y. Jung,et al.  Controlled Doping of Vacancy-Containing Few-Layer MoS2 via Highly Stable Thiol-Based Molecular Chemisorption. , 2015, ACS nano.

[4]  Ruhong Zhou,et al.  Tunable, Strain-Controlled Nanoporous MoS₂ Filter for Water Desalination. , 2016, ACS nano.

[5]  A. Patil,et al.  Aqueous Stabilization and Self‐Assembly of Graphene Sheets into Layered Bio‐Nanocomposites using DNA , 2009 .

[6]  K. Ariga,et al.  Layer-by-layer architectures of concanavalin A by means of electrostatic and biospecific interactions , 1995 .

[7]  G. Duesberg,et al.  Functionalization of Two-Dimensional MoS2 : On the Reaction Between MoS2 and Organic Thiols. , 2016, Angewandte Chemie.

[8]  Omid C Farokhzad,et al.  DNA Self-Assembly of Targeted Near-Infrared-Responsive Gold Nanoparticles for Cancer Thermo-Chemotherapy , 2012, Angewandte Chemie.

[9]  Y. Gogotsi,et al.  MoS2 Nanosheets Vertically Aligned on Carbon Paper: A Freestanding Electrode for Highly Reversible Sodium‐Ion Batteries , 2016 .

[10]  Warren C W Chan,et al.  Tuning the Drug Loading and Release of DNA‐Assembled Gold‐Nanorod Superstructures , 2016, Advanced materials.

[11]  Jonathan N. Coleman,et al.  Basal-Plane Functionalization of Chemically Exfoliated Molybdenum Disulfide by Diazonium Salts. , 2015, ACS nano.

[12]  Lehui Lu,et al.  MoS2 Nanosheets with Widened Interlayer Spacing for High‐Efficiency Removal of Mercury in Aquatic Systems , 2016 .

[13]  Chor Yong Tay,et al.  Nature-inspired DNA nanosensor for real-time in situ detection of mRNA in living cells. , 2015, ACS nano.

[14]  Hong Qun Luo,et al.  Emerging 0D Transition-Metal Dichalcogenides for Sensors, Biomedicine, and Clean Energy. , 2017, Small.

[15]  Katsuhiko Ariga,et al.  Self-Construction from 2D to 3D: One-Pot Layer-by-Layer Assembly of Graphene Oxide Sheets Held Together by Coordination Polymers. , 2016, Angewandte Chemie.

[16]  M. Longo,et al.  Novel near-infrared emission from crystal defects in MoS2 multilayer flakes , 2016, Nature Communications.

[17]  Chor Yong Tay,et al.  Reality Check for Nanomaterial‐Mediated Therapy with 3D Biomimetic Culture Systems , 2016 .

[18]  Zhaolin Li,et al.  MoS2 Nanosheets Vertically Grown on Graphene Sheets for Lithium-Ion Battery Anodes. , 2016, ACS nano.

[19]  Chunhai Fan,et al.  Single-layer MoS2-based nanoprobes for homogeneous detection of biomolecules. , 2013, Journal of the American Chemical Society.

[20]  Chor Yong Tay,et al.  Cellular processing and destinies of artificial DNA nanostructures. , 2016, Chemical Society reviews.

[21]  Hiroshi Sugiyama,et al.  Nature-Inspired Design of Smart Biomaterials Using the Chemical Biology of Nucleic Acids , 2016 .

[22]  B. Jonker,et al.  Exciton diamagnetic shifts and valley Zeeman effects in monolayer WS2 and MoS2 to 65 Tesla , 2015, Nature Communications.

[23]  Yury Gogotsi,et al.  Intercalation and delamination of layered carbides and carbonitrides , 2013, Nature Communications.

[24]  Xin Chen,et al.  Functionalization of Two‐Dimensional Transition‐Metal Dichalcogenides , 2016, Advanced materials.

[25]  M. I. Setyawati,et al.  Protecting microRNAs from RNase degradation with steric DNA nanostructures† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc01829g Click here for additional data file. , 2016, Chemical science.

[26]  Towards intrinsic charge transport in monolayer molybdenum disulfide by defect and interface engineering. , 2014, Nature communications.

[27]  N. Seeman,et al.  Programmable materials and the nature of the DNA bond , 2015, Science.

[28]  Mrinmoy De,et al.  Ligand conjugation of chemically exfoliated MoS2. , 2013, Journal of the American Chemical Society.

[29]  H. Luo,et al.  Size‐Dependent Optical Absorption of Layered MoS2 and DNA Oligonucleotides Induced Dispersion Behavior for Label‐Free Detection of Single‐Nucleotide Polymorphism , 2015 .

[30]  Takeshi Fujita,et al.  Covalent functionalization of monolayered transition metal dichalcogenides by phase engineering. , 2015, Nature chemistry.

[31]  H. Tian,et al.  Targeted Intracellular Production of Reactive Oxygen Species by a 2D Molybdenum Disulfide Glycosheet , 2016, Advanced materials.

[32]  Bo Chen,et al.  Single‐Layer Transition Metal Dichalcogenide Nanosheet‐Based Nanosensors for Rapid, Sensitive, and Multiplexed Detection of DNA , 2015, Advanced materials.

[33]  Katsuhiko Ariga,et al.  Layer-by-layer films of graphene and ionic liquids for highly selective gas sensing. , 2010, Angewandte Chemie.

[34]  Yuanyi Zheng,et al.  Injectable 2D MoS2‐Integrated Drug Delivering Implant for Highly Efficient NIR‐Triggered Synergistic Tumor Hyperthermia , 2015, Advanced materials.

[35]  H. Luo,et al.  Electrochemically induced Fenton reaction of few-layer MoS2 nanosheets: preparation of luminescent quantum dots via a transition of nanoporous morphology. , 2014, Nanoscale.

[36]  Zhuang Liu,et al.  Combined photothermal and photodynamic therapy delivered by PEGylated MoS2 nanosheets. , 2014, Nanoscale.

[37]  Layer-by-Layer Assembly for Graphene-Based Multilayer Nanocomposites: Synthesis and Applications , 2015 .

[38]  Jie Yu,et al.  High-throughput synthesis of single-layer MoS2 nanosheets as a near-infrared photothermal-triggered drug delivery for effective cancer therapy. , 2014, ACS nano.

[39]  Joseph J. Richardson,et al.  Technology-driven layer-by-layer assembly of nanofilms , 2015, Science.

[40]  X. Qu,et al.  Carbon Nanomaterials and DNA: from Molecular Recognition to Applications. , 2016, Accounts of chemical research.

[41]  Charlie Tsai,et al.  Activating and optimizing MoS2 basal planes for hydrogen evolution through the formation of strained sulphur vacancies. , 2016, Nature materials.

[42]  P. Laplace,et al.  Functionalization of liquid-exfoliated two-dimensional 2H-MoS2. , 2015, Angewandte Chemie.

[43]  Warren C. W. Chan,et al.  DNA-controlled dynamic colloidal nanoparticle systems for mediating cellular interaction , 2016, Science.

[44]  Zhen Gu,et al.  Enhanced anticancer efficacy by ATP-mediated liposomal drug delivery. , 2014, Angewandte Chemie.

[45]  Liang Cheng,et al.  Drug Delivery with PEGylated MoS2 Nano‐sheets for Combined Photothermal and Chemotherapy of Cancer , 2014, Advanced materials.

[46]  S. Louie,et al.  Optical spectrum of MoS2: many-body effects and diversity of exciton states. , 2013, Physical review letters.

[47]  Costas P. Grigoropoulos,et al.  High‐Performance Flexible Multilayer MoS2 Transistors on Solution‐Based Polyimide Substrates , 2016 .

[48]  Zhen Gu,et al.  ATP-triggered anticancer drug delivery , 2014, Nature Communications.

[49]  Y. Jeong,et al.  A drug-loaded aptamer-gold nanoparticle bioconjugate for combined CT imaging and therapy of prostate cancer. , 2010, ACS nano.

[50]  Jianping Xie,et al.  Low‐Dimensional Transition Metal Dichalcogenide Nanostructures Based Sensors , 2016 .

[51]  J. Coleman,et al.  Ultrafast saturable absorption of two-dimensional MoS2 nanosheets. , 2013, ACS nano.