Protein-assisted self-assembly of multifunctional nanoparticles

A bioengineering method for self-assembly of multifunctional superstructures with in-advance programmable properties has been proposed. The method employs two unique proteins, barnase and barstar, to rapidly join the structural components together directly in water solutions. The properties of the superstructures can be designed on demand by linking different agents of various sizes and chemical nature, designated for specific goals. As a proof of concept, colloidally stable trifunctional structures have been assembled by binding together magnetic particles, quantum dots, and antibodies using barnase and barstar. The assembly has demonstrated that the bonds between these proteins are strong enough to hold macroscopic (5 nm–3 μm) particles together. Specific interaction of such superstructures with cancer cells resulted in fluorescent labeling of the cells and their responsiveness to magnetic field. The method can be used to join inorganic moieties, organic particles, and single biomolecules for synergistic use in different applications such as biosensors, photonics, and nanomedicine.

[1]  K. Lukyanov,et al.  Targeting cancer cells by using an antireceptor antibody-photosensitizer fusion protein , 2009, Proceedings of the National Academy of Sciences.

[2]  Huan-Cheng Chang,et al.  Mass production and dynamic imaging of fluorescent nanodiamonds. , 2008, Nature nanotechnology.

[3]  Bernhard Gleich,et al.  Targeted delivery of magnetic aerosol droplets to the lung , 2007, Nature Nanotechnology.

[4]  D. Slamon.  Studies of the HER-2/neu proto-oncogene in human breast cancer. , 1990, Cancer investigation.

[5]  Sergey M Deyev,et al.  Multivalency: the hallmark of antibodies used for optimization of tumor targeting by design. , 2008, BioEssays : news and reviews in molecular, cellular and developmental biology.

[6]  Taeghwan Hyeon,et al.  Multifunctional nanostructured materials for multimodal imaging, and simultaneous imaging and therapy. , 2009, Chemical Society reviews.

[7]  Matthias Stuber,et al.  Magnetic resonance–guided, real-time targeted delivery and imaging of magnetocapsules immunoprotecting pancreatic islet cells , 2007, Nature Medicine.

[8]  Vincent M. Rotello,et al.  Magnetic assembly of colloidal superstructures with multipole symmetry , 2009, Nature.

[9]  M. Howarth,et al.  Targeting quantum dots to surface proteins in living cells with biotin ligase. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[10]  A. Paul Alivisatos,et al.  Pyramidal and chiral groupings of gold nanocrystals assembled using DNA scaffolds. , 2009, Journal of the American Chemical Society.

[11]  May D. Wang,et al.  In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags , 2008, Nature Biotechnology.

[12]  Robert Langer,et al.  Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA–PEG nanoparticles , 2008, Proceedings of the National Academy of Sciences.

[13]  G. V. Lutsenko,et al.  Barnase as a New Therapeutic Agent Triggering Apoptosis in Human Cancer Cells , 2008, PloS one.

[14]  James H. Adair,et al.  Encapsulation of organic molecules in calcium phosphate nanocomposite particles for intracellular imaging and drug delivery. , 2008, Nano letters.

[15]  Shouheng Sun,et al.  Magnetic Nanoparticles: Synthesis, Functionalization, and Applications in Bioimaging and Magnetic Energy Storage , 2009 .

[16]  Petr I. Nikitin,et al.  Quantitative real-time in vivo detection of magnetic nanoparticles by their nonlinear magnetization , 2008 .

[17]  A. Plückthun,et al.  Tumor Targeting of Mono-, Di-, and Tetravalent Anti-p185HER-2 Miniantibodies Multimerized by Self-associating Peptides* , 2001, The Journal of Biological Chemistry.

[18]  R. Hartley.  Barnase-barstar interaction. , 2001, Methods in enzymology.

[19]  Jeffrey I. Zink,et al.  Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery , 2010, BiOS.

[20]  Petr I. Nikitin,et al.  Highly sensitive room-temperature method of non-invasive in vivo detection of magnetic nanoparticles , 2009 .

[21]  T. Pellegrino,et al.  Fluorescent-Magnetic Hybrid Nanostructures: Preparation, Properties, and Applications in Biology , 2007, IEEE Transactions on NanoBioscience.

[22]  Y. Yarden,et al.  Untangling the ErbB signalling network , 2001, Nature Reviews Molecular Cell Biology.

[23]  A. López-Requena,et al.  In vivo site-specific biotinylation of proteins within the secretory pathway using a single vector system , 2008, BMC biotechnology.

[24]  O. Gang,et al.  Controllable g5p-protein-directed aggregation of ssDNA-gold nanoparticles. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[25]  A. Fersht,et al.  Protein-protein recognition: crystal structural analysis of a barnase-barstar complex at 2.0-A resolution. , 1994, Biochemistry.

[26]  S. Gambhir,et al.  Quantum Dots for Live Cells, in Vivo Imaging, and Diagnostics , 2005, Science.

[27]  Tymish Y. Ohulchanskyy,et al.  A general approach to binary and ternary hybrid nanocrystals. , 2006, Nano letters.

[28]  O. Stremovskiy,et al.  Expression of single-chain antibody-barstar fusion in plants. , 2007, Biochimie.

[29]  A. Fersht,et al.  Rapid, electrostatically assisted association of proteins , 1996, Nature Structural Biology.

[30]  Andreas Plückthun,et al.  Design of multivalent complexes using the barnase·barstar module , 2003, Nature Biotechnology.

[31]  V. Prassolov,et al.  Binase induces apoptosis of transformed myeloid cells and does not induce T-cell immune response. , 2007, Biochemical and biophysical research communications.

[32]  Monty Liong,et al.  Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery. , 2008, ACS nano.