2D Superparamagnetic Tantalum Carbide Composite MXenes for Efficient Breast-Cancer Theranostics

Background: The emergence of two-dimensional MXenes has spurred their versatile applications in broad fields, but the exploring of novel MXene-based family members and their potential applications in theranostic nanomedicine (concurrent diagnostic imaging and therapy) have been rarely explored. In this work, we report the construction of a novel superparamagnetic MXene-based theranostic nanoplatform for efficient breast-cancer theranostics, which was based on intriguing tantalum carbide (Ta4C3) MXene and its further rational surface-superparamagnetic iron-oxide functionalization (Ta4C3-IONP-SPs composite MXenes) for efficient breast-cancer theranostic. Methods: The fabrication of ultrathin Ta4C3 nanosheets was based on an exfoliation strategy and superparamagnetic iron oxide nanoparticles were in-situ grown onto the surface of Ta4C3 MXene according to the redox reaction of MXene. Ta4C3-IONP MXenes were modified with soybean phospholipid (SP) to guarantee high stability in physiological conditions. The photothermal therapy, contrast-enhanced CT, T2-weighted magnetic resonance imaging and the high biocompatibility of these composite nanosheets have also been evaluated in vitro at cellular level and in vivo on mice breast tumor allograft tumor model. Results: The Ta component of Ta4C3-IONP-SPs exhibits high performance for contrast-enhanced CT imaging because of its high atomic number and high X-ray attenuation coefficient, and the integrated superparamagnetic IONPs act as excellent contrast agents for T2-weighted magnetic resonance imaging. Especially, these Ta4C3-IONP-SPs composite nanosheets with high photothermal-conversion efficiency (η: 32.5%) has achieved complete tumor eradication without reoccurrence, verifying their highly efficient breast-tumor photo-ablation performance. Conclusion: This work not only significantly broadens the biomedical applications of MXene-based nanoplatforms (Ta4C3 MXene) by exploring their novel family members and further functionalization strategies (magnetic functionalization in this work), but also provides a novel and efficient theranostic nanoplatform for efficient breast-cancer theranostics.

[1]  Yury Gogotsi,et al.  Mxenes: A New Family of Two-Dimensional Materials and Its Application As Electrodes for Li and Na-Ion Batteries , 2015 .

[2]  Lianzhou Wang,et al.  Two-dimensional non-carbonaceous materials-enabled efficient photothermal cancer therapy , 2016 .

[3]  Sung Hun Kim,et al.  Diagnostic Performance of and Breast Tissue Changes at Early Breast MR Imaging Surveillance in Women after Breast Conservation Therapy. , 2017, Radiology.

[4]  Andre K. Geim,et al.  The rise of graphene. , 2007, Nature materials.

[5]  Yury Gogotsi,et al.  Two‐Dimensional Nanocrystals Produced by Exfoliation of Ti3AlC2. , 2011 .

[6]  Peng Wang,et al.  MXene Ti3C2: An Effective 2D Light-to-Heat Conversion Material. , 2017, ACS nano.

[7]  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.

[8]  Shaojun Guo,et al.  Black Phosphorus Nanosheet‐Based Drug Delivery System for Synergistic Photodynamic/Photothermal/Chemotherapy of Cancer , 2017, Advanced materials.

[9]  Andre K. Geim,et al.  Two-dimensional atomic crystals. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[10]  Liang Cheng,et al.  Functional nanomaterials for phototherapies of cancer. , 2014, Chemical reviews.

[11]  Taeghwan Hyeon,et al.  Nano‐Sized CT Contrast Agents , 2013, Advanced materials.

[12]  Yury Gogotsi,et al.  25th Anniversary Article: MXenes: A New Family of Two‐Dimensional Materials , 2014, Advanced materials.

[13]  V. Presser,et al.  Two‐Dimensional Nanocrystals Produced by Exfoliation of Ti3AlC2 , 2011, Advanced materials.

[14]  L. Dai,et al.  Oxidizing metal ions with graphene oxide: the in situ formation of magnetic nanoparticles on self-reduced graphene sheets for multifunctional applications. , 2011, Chemical communications.

[15]  C. Mirkin,et al.  Controlling anisotropic nanoparticle growth through plasmon excitation , 2003, Nature.

[16]  Yury Gogotsi,et al.  Two-dimensional transition metal carbides. , 2012, ACS nano.

[17]  Younan Xia,et al.  A plasmon-assisted optofluidic (PAOF) system for measuring the photothermal conversion efficiencies of gold nanostructures and controlling an electrical switch. , 2013, Angewandte Chemie.

[18]  Liangzhu Feng,et al.  Intelligent Albumin–MnO2 Nanoparticles as pH‐/H2O2‐Responsive Dissociable Nanocarriers to Modulate Tumor Hypoxia for Effective Combination Therapy , 2016, Advanced materials.

[19]  C Jeffrey Brinker,et al.  Chemically exfoliated MoS2 as near-infrared photothermal agents. , 2012, Angewandte Chemie.

[20]  Zhuang Liu,et al.  Degradable Vanadium Disulfide Nanostructures with Unique Optical and Magnetic Functions for Cancer Theranostics. , 2017, Angewandte Chemie.

[21]  Chang E. Ren,et al.  Antibacterial Activity of Ti3C2Tx MXene , 2016 .

[22]  Minshen Zhu,et al.  Photoluminescent Ti3C2 MXene Quantum Dots for Multicolor Cellular Imaging , 2017, Advanced materials.

[23]  N. Dubrawsky.  Cancer statistics , 1989, CA: a cancer journal for clinicians.

[24]  Jie Yu,et al.  Smart MoS2/Fe3O4 Nanotheranostic for Magnetically Targeted Photothermal Therapy Guided by Magnetic Resonance/Photoacoustic Imaging , 2015, Theranostics.

[25]  Yaqi Cai,et al.  A novel Fe3O4–graphene–Au multifunctional nanocomposite: green synthesis and catalytic application , 2012 .

[26]  Zhouyi Guo,et al.  Fabrication of Graphene and AuNP Core Polyaniline Shell Nanocomposites as Multifunctional Theranostic Platforms for SERS Real-time Monitoring and Chemo-photothermal Therapy , 2016, Theranostics.

[27]  H. Dai,et al.  Chemically Derived, Ultrasmooth Graphene Nanoribbon Semiconductors , 2008, Science.

[28]  P. Jacobs,et al.  Physical and chemical properties of superparamagnetic iron oxide MR contrast agents: ferumoxides, ferumoxtran, ferumoxsil. , 1995, Magnetic resonance imaging.

[29]  Yasuyoshi Watanabe,et al.  [Molecular imaging for drug development]. , 2007, Brain and nerve = Shinkei kenkyu no shinpo.

[30]  Yury Gogotsi,et al.  Conductive two-dimensional titanium carbide ‘clay’ with high volumetric capacitance , 2014, Nature.

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

[32]  Xiaochuan Pan,et al.  Anniversary Paper: Development of x-ray computed tomography: The role of Medical Physics and AAPM from the 1970s to present. , 2008, Medical physics.

[33]  C. Zhi,et al.  Ultrathin MXene‐Micropattern‐Based Field‐Effect Transistor for Probing Neural Activity , 2016, Advanced materials.

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

[35]  Liang Cheng,et al.  Organic-Base-Driven Intercalation and Delamination for the Production of Functionalized Titanium Carbide Nanosheets with Superior Photothermal Therapeutic Performance. , 2016, Angewandte Chemie.

[36]  A. Jemal,et al.  Cancer statistics, 2016 , 2016, CA: a cancer journal for clinicians.

[37]  P. Chu,et al.  Ultrasmall Black Phosphorus Quantum Dots: Synthesis and Use as Photothermal Agents. , 2015, Angewandte Chemie.

[38]  Yury Gogotsi,et al.  2D metal carbides and nitrides (MXenes) for energy storage , 2017 .

[39]  S. Zick,et al.  Clinical practice guidelines on the evidence‐based use of integrative therapies during and after breast cancer treatment , 2017, CA: a cancer journal for clinicians.

[40]  P. Fitzgerald,et al.  Synthesis, characterization, and computed tomography imaging of a tantalum oxide nanoparticle imaging agent. , 2010, Chemical communications.

[41]  H. Dai,et al.  Ultrasmall reduced graphene oxide with high near-infrared absorbance for photothermal therapy. , 2011, Journal of the American Chemical Society.

[42]  Kai Yang,et al.  Multimodal Imaging Guided Photothermal Therapy using Functionalized Graphene Nanosheets Anchored with Magnetic Nanoparticles , 2012, Advanced materials.

[43]  Yu Chen,et al.  Two-Dimensional Ultrathin MXene Ceramic Nanosheets for Photothermal Conversion. , 2017, Nano letters.

[44]  M. Hoepfner,et al.  Microscale Heat Transfer Transduced by Surface Plasmon Resonant Gold Nanoparticles. , 2007, The journal of physical chemistry. C, Nanomaterials and interfaces.

[45]  Sungho Jin,et al.  Magnetic nanoparticles for theragnostics. , 2009, Advanced drug delivery reviews.

[46]  Matthew G. Panthani,et al.  Copper selenide nanocrystals for photothermal therapy. , 2011, Nano letters.

[47]  X. Qu,et al.  New Horizons for Diagnostics and Therapeutic Applications of Graphene and Graphene Oxide , 2013, Advanced materials.

[48]  B. Hong,et al.  Biomedical applications of graphene and graphene oxide. , 2013, Accounts of chemical research.

[49]  Lianzhou Wang,et al.  Two‐Dimensional Graphene Analogues for Biomedical Applications , 2015 .