Nanocrystal facet modulation to enhance transferrin binding and cellular delivery

Binding of biomolecules to crystal surfaces is critical for effective biological applications of crystalline nanomaterials. Here, we present the modulation of exposed crystal facets as a feasible approach to enhance specific nanocrystal–biomolecule associations for improving cellular targeting and nanomaterial uptake. We demonstrate that facet-engineering significantly enhances transferrin binding to cadmium chalcogenide nanocrystals and their subsequent delivery into cancer cells, mediated by transferrin receptors, in a complex biological matrix. Competitive adsorption experiments coupled with theoretical calculations reveal that the (100) facet of cadmoselite and (002) facet of greenockite preferentially bind with transferrin via inner-sphere thiol complexation. Molecular dynamics simulation infers that facet-dependent transferrin binding is also induced by the differential affinity of crystal facets to water molecules in the first solvation shell, which affects access to exposed facets. Overall, this research underlines the promise of facet engineering to improve the efficacy of crystalline nanomaterials in biological applications. Modulation of exposed crystal facets enhances transferrin binding to chalcogenide nanocrystals and their subsequent delivery into cancer cells. Facet-dependent protein binding occurs through inner-sphere thiol complexation and is affected by the structure of the first solvation shell.

[1]  H. Monkhorst,et al.  SPECIAL POINTS FOR BRILLOUIN-ZONE INTEGRATIONS , 1976 .

[2]  Ezequiel Bernabeu,et al.  The transferrin receptor and the targeted delivery of therapeutic agents against cancer. , 2012, Biochimica et biophysica acta.

[3]  Berk Hess,et al.  LINCS: A linear constraint solver for molecular simulations , 1997, J. Comput. Chem..

[4]  Jincai Zhao,et al.  Facet-Dependent Cr(VI) Adsorption of Hematite Nanocrystals. , 2016, Environmental science & technology.

[5]  J. Madura,et al.  Molecular recognition and binding of thermal hysteresis proteins to ice , 2000, Journal of molecular recognition : JMR.

[6]  I. Willner,et al.  Semiconductor quantum dots for bioanalysis. , 2008, Angewandte Chemie.

[7]  R. Sperling,et al.  Surface modification, functionalization and bioconjugation of colloidal inorganic nanoparticles , 2010, Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences.

[8]  E. Del Gado,et al.  Low-Index ZnO Crystal Plane-Specific Binding Behavior of Whole Immunoglobulin G Proteins. , 2015, Langmuir : the ACS journal of surfaces and colloids.

[9]  Berk Hess,et al.  LINCS: A linear constraint solver for molecular simulations , 1997 .

[10]  Hua Zhang,et al.  Controlled growth of high-density CdS and CdSe nanorod arrays on selective facets of two-dimensional semiconductor nanoplates. , 2016, Nature chemistry.

[11]  G. Kresse,et al.  From ultrasoft pseudopotentials to the projector augmented-wave method , 1999 .

[12]  Z. Qian,et al.  The role of the transferrin-transferrin-receptor system in drug delivery and targeting. , 2002, Trends in pharmacological sciences.

[13]  Mark J. Biggs,et al.  Molecular-level understanding of protein adsorption at the interface between water and a strongly interacting uncharged solid surface. , 2014, Journal of the American Chemical Society.

[14]  Kresse,et al.  Efficient iterative schemes for ab initio total-energy calculations using a plane-wave basis set. , 1996, Physical review. B, Condensed matter.

[15]  K Schulten,et al.  VMD: visual molecular dynamics. , 1996, Journal of molecular graphics.

[16]  S. Nie,et al.  Quantum dot bioconjugates for ultrasensitive nonisotopic detection. , 1998, Science.

[17]  Mark E. Davis,et al.  Mechanism of active targeting in solid tumors with transferrin-containing gold nanoparticles , 2009, Proceedings of the National Academy of Sciences.

[18]  Wei Chen,et al.  Facet Energy and Reactivity versus Cytotoxicity: The Surprising Behavior of CdS Nanorods. , 2016, Nano letters.

[19]  Iseult Lynch,et al.  Designing the nanoparticle-biomolecule interface for "targeting and therapeutic delivery". , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[20]  W. L. Jorgensen,et al.  Comparison of simple potential functions for simulating liquid water , 1983 .

[21]  K. Mopper,et al.  Field method for determination of traces of thiols in natural waters , 1990 .

[22]  Delyan R. Hristov,et al.  Mapping of Molecular Structure of the Nanoscale Surface in Bionanoparticles. , 2017, Journal of the American Chemical Society.

[23]  P. Sagayaraj,et al.  Structural and optical property studies of CdSe crystalline nanorods synthesized by a solvothermal method , 2009 .

[24]  Chenguo Hu,et al.  Water-induced structure phase transition of CdSe nanocrystals in composite hydroxide melts , 2010 .

[25]  Philip M. Kelly,et al.  Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface. , 2013, Nature nanotechnology.

[26]  Elodie Boisselier,et al.  Gold nanoparticles in nanomedicine: preparations, imaging, diagnostics, therapies and toxicity. , 2009, Chemical Society reviews.

[27]  R. Zhou,et al.  Facet-regulated adhesion of double-stranded DNA on palladium surfaces. , 2019, Nanoscale.

[28]  T. Xia,et al.  Understanding biophysicochemical interactions at the nano-bio interface. , 2009, Nature materials.

[29]  J. Zimmerman,et al.  Preferential adsorption of selenium oxyanions onto {1 1 0} and {0 1 2} nano-hematite facets. , 2019, Journal of colloid and interface science.

[30]  Peter M. Kasson,et al.  GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit , 2013, Bioinform..

[31]  Baojuan Xi,et al.  CdS Hierarchical Nanostructures with Tunable Morphologies: Preparation and Photocatalytic Properties , 2010 .

[32]  W. Han,et al.  Facet-Specific Assembly of Proteins on SrTiO3 Polyhedral Nanocrystals , 2014, Scientific Reports.

[33]  Jingyuan Li,et al.  Revealing the binding structure of the protein corona on gold nanorods using synchrotron radiation-based techniques: understanding the reduced damage in cell membranes. , 2013, Journal of the American Chemical Society.

[34]  Kristin A. Persson,et al.  Commentary: The Materials Project: A materials genome approach to accelerating materials innovation , 2013 .

[35]  Korin E. Wheeler,et al.  Silver nanoparticle protein corona composition compared across engineered particle properties and environmentally relevant reaction conditions , 2014 .

[36]  H. Hsu-Kim,et al.  Precipitation and growth of zinc sulfide nanoparticles in the presence of thiol-containing natural organic ligands. , 2008, Environmental science & technology.

[37]  Thierry Cloitre,et al.  Insights on the Facet Specific Adsorption of Amino Acids and Peptides toward Platinum , 2013, J. Chem. Inf. Model..

[38]  Stefan Grimme,et al.  Semiempirical GGA‐type density functional constructed with a long‐range dispersion correction , 2006, J. Comput. Chem..

[39]  LarssonPer,et al.  GROMACS 4.5 , 2013 .

[40]  D. Lelie,et al.  DNA-guided crystallization of colloidal nanoparticles , 2008, Nature.

[41]  Gerrit Groenhof,et al.  GROMACS: Fast, flexible, and free , 2005, J. Comput. Chem..

[42]  Berk Hess,et al.  GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers , 2015 .

[43]  Kemin Wang,et al.  Aptazyme-Gold Nanoparticle Sensor for Amplified Molecular Probing in Living Cells. , 2016, Analytical chemistry.

[44]  T. Darden,et al.  Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems , 1993 .

[45]  Force Field Parametrization of Colloidal CdSe Nanocrystals Using an Adaptive Rate Monte Carlo Optimization Algorithm. , 2017, Journal of chemical theory and computation.

[46]  E. Tajkhorshid,et al.  Structural basis for iron piracy by pathogenic Neisseria , 2012, Nature.

[47]  R. Dror,et al.  Improved side-chain torsion potentials for the Amber ff99SB protein force field , 2010, Proteins.

[48]  Rajesh Singh,et al.  Nanoparticle-based targeted drug delivery. , 2009, Experimental and molecular pathology.

[49]  Denis J. Evans,et al.  The Nose–Hoover thermostat , 1985 .

[50]  S. Nie,et al.  Self-assembled nanoparticle probes for recognition and detection of biomolecules. , 2002, Journal of the American Chemical Society.

[51]  Hafner,et al.  Ab initio molecular dynamics for open-shell transition metals. , 1993, Physical review. B, Condensed matter.

[52]  Zak E. Hughes,et al.  Facet-Specific Adsorption of Tripeptides at Aqueous Au Interfaces: Open Questions in Reconciling Experiment and Simulation. , 2017, Langmuir : the ACS journal of surfaces and colloids.

[53]  J. Raymond,et al.  Adsorption inhibition as a mechanism of freezing resistance in polar fishes. , 1977, Proceedings of the National Academy of Sciences of the United States of America.