ABSTRACT
6. Perspective
Protein-based nanomaterials and nanotechnology have revolutionized many important areas in molecular biology and biomedicine, especially in the design and manipulation of proteins, their higher-order assembly and their biomedical applications at the molecular and cellular level.
The marriage of molecular biology and nanotechnology opens up the possibility of manipulating atoms, molecules and structures at single- molecule and sub-molecular levels, with the potential for a wide spectrum of applications. However, the areas of protein-based nanomaterials are still in their early age of development, because our understanding of protein universe is still rather limited. Perhaps the most exciting perspective is that the protein nanomaterials will evolve into a new world of programmable nanoarchitecture and nanomachines with highly defi ned properties and functionality. To this end, a number of challenges remain to be addressed.
First, there are innumerous proteins whose structures and dynamics remain unknown. Even for most known protein structures, their physiological dynamics and functional interactions with other proteins remain elusive.
It is not yet fully understood how other protein nanomachines existing in nature work energetically and biochemically in detail. For example, there are no high-resolution structures for the full -length complexes of bacterial fl agellar rotor, making it unclear how to engineer these highly effi cient, elegant nanomachines reversely. Second, the computational tools developed over the last several decades in predicting proteins structure is not yet capable of predicting sophisticated complex structures or quaternary structures, which are required to build higher-order artifi cial protein nanomachines and nanoarchitectures. Third, there is still lack of technology and tools to characterize the kinetics and dynamics of working complex nanomachines at the atomic level, leaving the energetic mechanism of most protein nanomachines not fully appreciated. The most recent development of cryo-electron microscopy implies such a possibility; but its technical capability awaits further growth to address this challenge. Finally, it remains to be answered how the building blocks of engineered protein nano-engines are assembled into higher-order nanoscale system with smart properties through bottom-up approaches. Addressing all these challenges will mostly require highly multidisciplinary and interdisciplinary studies that combine a wide spectrum of exploratory technologies and tools. The future technology advancement at the interface between material sciences and molecular structural biology, such as de novo protein prediction, single- molecule cryo-electron microscopy and super-resolution light microscopy, will hopefully provide essential tool boxes and practical solutions to design, characterize, and innovate programmable smart protein nanomaterials in greater detail, magnitude and scale.
References
Alberts, B., A. Johnson, J. Lewis, M. Raff and K. Roberts. 2007. Molecular Biology of the Cell.
Garland Science, New York.
Allegretti, M., N. Klusch, D.J. Mills, J. Vonck, W. Kuhlbrandt and K.M. Davies. 2015. Horizontal membrane-intrinsic -helices in the stator a-subunit of an F-type ATP synthase. Nature doi:10.1038/nature14185.
Alushin, G.M., V.H. Ramey, S. Pasqualato, D.A. Ball, N. Grigorieff, A. Musacchio and E. Nogales. 2010. The Ndc80 kinetochore complex forms oligomeric arrays along microtubules. Nature 467: 805–810.
Anfi nsen, C.B. 1973. Principles that govern the folding of protein chains. Science 181: 223–230.
Anfi nsen, C.B. and E. Haber. 1961. Studies on the reduction and re-formation of protein disulfi de bonds. J. Biol. Chem. 236: 1361–1363.
Arndt, K.M. and K.M. Muller. 2007. Protein Engineering Protocols. Humana Press, Totowa, New Jersey.
Ban, N., P. Nissen, J. Hansen, P. Moore and T. Steitz. 2000. The complete atomic structure of the large ribosomal subunit at 2.4 Å resolution. Science 289: 905–20.
Barrick, J.E., D.S. Yu, S.H. Yoon, H. Jeong, T.K. Oh, D. Schneider, R.E. Lenski and J.F. Kim.
2009. Genome evolution and adaptation in a long-term experiment with Escherichia coli.
Nature 461: 1243–1247.
Berneche, S. and B. Roux. 2001. Energetics of ion conduction through the K+ channel. Nature 414: 73–77.
Bershitsky, S.Y., A.K. Tsaturyan, O.N. Bershitskaya, G.I. Mashanov, P. Brown, R. Burns and M.A. Ferenczi. 1997. Muscle force is generated by myosin heads stereospecifi cally attached to actin. Nature 388: 186–190.
Block, S.M. and H.C. Berg. 1984. Successive incorporation of force-generating units in the bacterial rotary motor. Nature 309: 470–473.
Branden, C. and J. Tooze. 1991. Introduction to Protein Structure. Garland, New York.
Brodin, J.D., X.I. Ambroggio, C. Tang, K.N. Parent, T.S. Baker and F.A. Tezcan. 2012. Metal- directed, chemically tunable assembly of one-, two- and three-dimensional crystalline protein arrays. Nature Chem. 4: 375–382.
Caspar, D.L.D. and A. Klug. 1962. Physical principles in the construction of regular viruses.
Q. Biol. 27: 1–24.
Clarke, J., H.C. Wu, L. Jayasinghe, A. Patel, S. Reid and H. Bayley. 2009. Continuous base identification for single-molecule nanopore DNA sequencing. Nat. Nanotechnol.
4: 265–270.
Dahiyat, B.I. and S.L. Mayo. 1997. De novo protein design: fully automated sequence selection.
Science 278: 82–87.
Dalby, P.A. 2011. Strategy and success for the directed evolution of enzymes. Curr. Opin.
Struct. Biol. 21: 473–480.
de Loubresse Garreau, N., I. Prokhorova, W. Holtkamp, M.V. Rodnina, G. Yusupova and M. Yusupov. 2014. Structural basis for the inhibition of the eukaryotic ribosome. Nature 513: 517–522.
Doyle, D.A., J. Morais Cabral, R.A. Pfuetzner, A. Kuo, J.M. Gulbis, S.L. Cohen, B.T. Chait and R. MacKinnon. 1998. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280: 68–77.
Ellis-Behnke, R.G., Y.X. Liang, S.W. You, D.K.C. Tay, S. Zhang, K.F. So and G.E. Schneider. 2006.
Nano neuro knitting: Peptide nanofi ber scaffold for brain repair and axon regeneration with functional return of vision. Proc. Natl. Acad. Sci. USA 103: 5054–5059.
Fletcher, D.A. and D. Mullins. 2010. Cell mechanics and the cytoskeleton 463: 485–492.
Fuchs, E. and D.W. Cleveland. 1998. A structural scaffolding of intermediate fi laments in health and disease. Science 279: 514–519.
Galland, R., P. Leduc, C. Guerin, D. Peyrade, L. Blanchoin and M. Thery. 2013. Fabrication of three-dimensional electrical connections by means of directed actin self-organization.
Nat. Mater. 12: 416–421.
Gee, M.A., J.E. Heuser and R.B. Vallee. 1997. An extended microtubule-binding structure within the dynein motor domain. Nature 390: 636–639.
Gotte, L., M.G. Giro, D. Volpin and R.W. Horne. 1974. The ultrastructural organization of elastin. J. Ultrastruct. Res. 46: 23–33.
Gotte, L., D. Volpin, R.W. Horne and M. Mammi. 1976. Electron microscopy and optical diffraction of elastin. Micron 7: 95–102.
Green, M.R. 2006. Abraxane(R), a novel Cremophor(R)-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer. Annals of Oncology 17: 1263–1268.
Gunning, P.W., U. Ghoshdastider, S. Whitaker, D. Popp and R.C. Robinson. 2015. The evolution of compositionally and functionally distinct actin fi laments. J. Cell Sci. doi: 10.1242/
jcs.165563.
Hanukoglu, I. and E. Fuchs. 1982. The cDNA sequence of a human epidermal keratin:
divergence of sequence but conservation of structure among intermediate fi lament proteins. Cell 31: 243–252.
Harbury, P.B., J.J. Plecs, B. Tidor, T. Alber and P.S. Kim. 1998. High-resolution protein design with backbone freedom. Science 282: 1462–7.
Hermann, H., H. Bar, L. Kreplak, S.V. Strelkov and U. Aebi. 2007. Intermediate fi laments: from cell architecture to nanomechanics. Nat. Rev. Mol. Cell Biol. 8: 562–573.
Hille, B. 2001. Ion channels of excitable membranes. Sinauer Associates, Sunderland, Massachusetts.
Hoersch, D., S.H. Roh, W. Chiu and T. Kortemme. 2013. Reprogramming an ATP-driven protein machine into a light-gated nanocage. Nat. Nanotechnol. 8: 928–932.
Hu, C., M. Ahemed, T.J. Melia, T.H. Sollner, T. Mayer and J.E. Rothman. 2003. Fusion of cells by fl ipped SNAREs. Science 300: 1745–1749.
Hudalla, G.A., T. Sun, J.Z. Gasiorowski, H. Han, Y.F. Tian, A.S. Chong and J.H. Collier. 2014.
Gradated assembly of multiple proteins into supramolecular nanomaterials. Nat. Mater.
13: 829–836.
Ishii, D., K. Kinbara, Y. Ishida, N. Ishii, M. Okochi, M. Yohda and T. Aida. 2003. Chaperonin- mediated stabilization and ATP-triggered release of semiconductor nanoparticles. Nature 423: 628–632.
Itoh, H., A. Takahashi, K. Adachi, H. Noji, R. Yasuda, M. Yoshida and K. Kinosita. 2004.
Mechanically driven ATP synthesis by F1-ATPase. Nature 427: 465–468.
Nelson, D. 2008. Lehininger Principles of Biochemistry. W.H. Freeman and Company, New York.
Jentsch, T.J., C.A. Hubner and J.C. Fuhrmann. 2004. Ion channels: Function unraveled by dysfunction. Nat. Cell Biol. 6: 1039–1047.
Jiang, Y., V. Ruta, J. Chen, A. Lee and R. MacKinnon. 2003. The principle of gating charge movement in a voltage-dependent K+ channel. Nature 423: 42–48.
Johnson, J.E. and J.A. Speir. 2009. Desk Encyclopedia of General Virology. pp. 115–123.
Academic Press, Boston.
King, N.P., W. Sheffl er, M.R. Sawaya, B.S. Vollmar, J.P. Sumida, I. Andre, T. Gonen, T.O. Yeates and D. Baker. 2012. Computational design of self-assembling protein nanomaterials with atomic level accuracy. Science 336: 1171–1174.
King, N.P., J.B. Bale, W. Sheffl er, D.E. McNamara, S. Gonen, T. Gonen, T.O. Yeates and D. Baker. 2014. Accurate design of co-assembling multi-component protein nanomaterials.
Nature 510: 103–108.
Kon, T., T. Oyama, R. Shimo-Kon, K. Imamula, T. Shima, K. Sutoh and G. Kurisu. 2012. The 2.8 Å crystal structure of the dynein motor domain. Nature 484: 345–350.
Kuhlman, B., G. Dantas, G.C. Ireton, G. Varani, B.L. Stoddard and D. Baker. 2003. Design of a novel globular protein fold with atomic-level accuracy. Science 302: 1364–1368.
Kull, F.J., E.P. Sablin, R. Lau, R.J. Fletterick and R.D. Vale. 1996. Crystal structure of the kinesin motor domain reveals a structural similarity to myosin. Nature 380: 550–555.
Lalwani, G., A.M. Henslee, B. Farshid, L. Lin, F.K. Kasper, Y.X. Qin, A.G. Mikos and B. Sitharaman. 2013. Two-dimensional nanostructure-reinforced biodegradable polymeric nanocomposites for bone tissue engineering. Biomacromolecules 14: 900–909.
Lau, W.C. and J.L. Rubinstein. 2012. Subnanometre-resolution structure of the intact Thermus thermophiles H+-driven ATP synthase. Nature 481: 214–218.
Leaver-Fay, A., M. Tyka, S.M. Lewis, O.F. Lange, J. Thompson, R. Jacak, K. Kaufman, P.D.
Renfrew, C.A. Smith, W. Sheffl er, I.W. Davis, S. Cooper, A. Treuille, D.J. Mandell, F.
Richter, Y.E. Ban, S.J. Fleishman, J.E. Corn, D.E. Kim, S. Lyskov, M. Berrondo, S. Mentzer, Z. Popović, J.J. Havranek, J. Karanicolas, R. Das, J. Meiler, T. Kortemme, J.J. Gray, B.
Kuhlman, D. Baker and P. Bradley. 2011. ROSETTA3: an object-oriented software suite for the simulation and design of macromolecules. Methods Enzymol. 487: 545–574.
Lee, J.H., J.H. Lee, Y.J. Lee and K.T. Nam. 2013. Protein/peptide based nanomaterials for energy application. Curr. Opin. Biotechnol. 24: 599–605.
Levinthal, C. 1968. Are there pathways for protein folding. Journal de Chimie Physique et de Physico-Chimie Biologique 65: 44–45.
Lewin, B., L. Cassimeris, V.R. Lingappa and G. Plopper. 2007. Cells. Jones and Bartlett Publishers, Sudbury, Massachusetts.
Lin, S.C., Y.C. Lo and H. Wu. 2010. Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling. Nature 465: 885–890.
Long, S.B., E.B. Campbell and R. MacKinnon. 2005a. Voltage sensor of Kv1.2: structural basis of electromechanical coupling. Science 309: 903–908.
Long, S.B., E.B. Campbell and R. MacKinnon. 2005b. Crystal structure of a mammalian voltage- dependent Shaker family K+ channel. Science 309: 897–903.
Lutz, S. 2010. Beyond directed evolution—semi-rational protein engineering and design. Curr.
Opin. Biotechnol. 21: 734–743.
MacBeath, G., P. Kast and D. Hilvert. 1998. Redesigning enzyme topology by directed evolution.
Science 279: 1958–1961.
Mao, Y., L. Wang, C. Gu, A. Herschhorn, S.H. Xiang, H. Haim, X. Yang and J. Sodroski. 2012.
Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer. Nat.
Struct. Mol. Biol. 19: 893–899.
Mao, Y., L. Wang, C. Gu, A. Herschhorn, A. Desormeaux, A. Finzi, S.H. Xiang and J.G. Sodroski.
2013. Molecular architecture of the uncleaved HIV-1 envelope glycoprotein trimer. Proc.
Natl. Acad. Sci. USA 110: 12438–12443.
Marco, M.D., S. Shamsuddin, K.A. Razak, A.A. Aziz, C. Devaux, E. Borghi, L. Levy and C. Sadun. 2010. Overview of the main methods used to combine proteins with nanosystems: absorption, bioconjugation and encapsulation. Int. J. Nanomedicine 5:
37–49.
Mathé, J., A. Aksimentiev, D.R. Nelson, K. Schulten and A. Meller. 2005. Orientation discrimination of single stranded DNA inside the α-hemolysin membrane channel. Proc.
Natl. Acad. Sci. USA 102: 12377–12382.
Mueckler, M., C. Caruso, S.A. Baldwin, M. Panico, I. Blench, H.R. Morris, W.J. Allard, G.E. Lienhard and H.F. Lodish. 1985. Sequence and structure of a human glucose transporter. Science 229: 941–945.
Muiznieks, L.D., A.S. Weiss and F.W. Keeley. 2010. Structural disorder and dynamics of elastin.
Biochem. Cell Biol. 88: 239–250.
Murail, R., D.J. Sharkey, J.L. Daiss and H.M. Murthy. 1998. Crystal structure of Taq DNA polymerase in complex with an inhibitory Fab: the Fab is directed against an intermediate in the helix-coil dynamics of the enzyme. Proc. Natl. Acad. Sci. USA 95: 12562–12567.
Nam, J.M., C.S. Thaxton and C.A. Mirkin. 2003. Nanoparticle-based bio-bar codes for the ultrasensitive detection of proteins. Science 301: 1884–1886.
Nogales, E. 2000. Structural insights into microtubule function. Annu. Rev. Biochem.
69: 277–302.
Noji, H., R. Yasuda, M. Yoshida and K. Kinosita, Jr. 1997. Direct observation of the rotation of F1-ATPase. Nature 386: 299–302.
Papapostolou, D., A.M. Smith, E.D.T. Atkins, S.J. Oliver, M.G. Ryadnov, L.C. Serpell and D.N. Woolfson. 2007. Engineering nanoscale order into a designed protein fi ber. Proc.
Natl. Acad. Sci. USA 104: 10853–10858.
Pepe, A., B. Bochicchio and A.M. Tamburro. 2007. Supramolecular organization of elastin and elastin-related nanostructured biopolymers. Nanomed. 2: 203–218.
Rayment, I., W.R. Rypniewski, K. Schmidt-Base, R. Smith, D.R. Tomchick, M.M. Benning, D.A. Winkelman, G. Wesenberg and H.M. Holden. 1993. Three-dimensional structure of myosin subfragment-1: A molecular motor. Science 261: 50–58.
Reymann, A.C., J.L. Martiel, T. Cambier, L. Blanchoin, R. Boujemaa-Paterski and M. Thery. 2010.
Nucleation geometry governs ordered actin networks structure. Nat. Mater. 9: 827–832.
Richardson, J.S. and D.C. Richardson. 1989. The de novo design of protein structures. Trends in Biochemical Sciences 14: 304–9.
Rodrigues-Larrea, D. and H. Bayley. 2013. Multistep protein unfolding during nanopore translocation. Nat. Nanotechnol. 8: 288–295.
Rondelez, Y., G. Tresset, T. Nakashima, Y. Kato-Yamada, H. Fujita, S. Takeuchi and H. Noji.
2005. Highly coupled ATP synthesis by F1-ATPase single molecules. Nature 433: 773–777.
Ryu, W.S., R.M. Berry and H.C. Berg. 2000. Torque-generating units of the fl agellar motor of Escherichia coli have a high duty ratio. Nature 403: 444–447.
Schluenzen, F., A. Tocilj, R. Zarivach, J. Harms, M. Gluehmann, D. Janell, A. Bashan, H. Bartels, I. Agmon, F. Franceschi and A. Yonath. 2000. Structure of functionally activated small ribosomal subunit at 3.3 Å resolution. Cell 102: 615–23.
Schnitzer, M.J. and S.M. Block. 1997. Kinesin hydrolyses one ATP per 8-nm step. Nature 388: 386–390.
Shingyoji, C., H. Higuchi, M. Yoshimura, E. Katayama and T. Yanagida. 1998. Dynein arms are oscillating force generators. Nature 393: 711–714.
Song, L., M.R. Hobaugh, C. Shustak, S. Cheley, H. Bayley and J.E. Gouaux. 1996. Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore. Science 274: 1859–1866.
Stock, D., A.G. Leslie and J.E. Walker. 1999. Molecular architecture of the rotary motor in ATP synthase. Science 286: 1700–1705.
Stuhmer, W., F. Conti, H. Suzuki, X.D. Wang, M. Noda, N. Yahagi, H. Kubo and S. Numa.
1989. Structural parts involved in activation and inactivation of the sodium channel.
Nature 339: 597–603.
Sutton, R.B., D. Fasshauer, R. Jahn and A.T. Brunger. 1998. Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution. Nature 395: 347–353.
Thomas, D.R., N.R. Francis, C. Xu and D.J. DeRosier. 2006. The three-dimensional structure of the fl agellar rotor from a clockwise-locked mutant of Salmonella enterica serovar Typhimurium. J. Bacteriol. 188: 7039–7048.
Toyoshima, C., M. Nakasako, H. Nomura and H. Ogawa. 2000. Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 Å resolution. Nature 405: 647–655.
Toyoshima, C. and H. Nomura. 2002. Structural changes in the calcium pump accompanying the dissociation of calcium. Nature 418: 605–611.
Urnavicius, L., K. Zhang, A.G. Diamant, C. Motz, M.A. Schlager, M. Yu, N.A. Patel, C.V. Robinson and A.P. Carter. 2015. The structure of the dynactin complex and its interaction with dynein. Science 347: 1441–1446.
Vale, R.D., T. Funatsu, D.W. Pierce, L. Romberg, Y. Harada and T. Yanagida. 1996. Direct observation of single kinesin molecules moving along microtubules. Nature 380: 451–453.
Vauthey, S., S. Santoso, H. Gong, N. Waston and S. Zhang. 2002. Molecular self-assembly of surfactant-like peptides to form nanotu bes and nanovesicles. Proc. Natl. Acad. Sci. USA 99: 5355–5360.
Veesler, D., T.S. Ng, A.K. Sendamarai, B.J. Eilers, C.M. Lawrence, S.M. Lok, M.J. Young, J.E. Johnson and C.Y. Fu. 2013. Atomic structure of the 75 MDa extremophile Sulfolobus turreted icosahedral virus determined by CryoEM and X-ray crystallography. Proc. Natl.
Acad. Sci. USA 110: 5504–5509.
Voigt, C.A., S. Kauffman and Z.G. Wang. 2000. Rational evolutionary design: the theory of in vitro protein evolution. Adv. Protein Chem. 55: 79–160.
Von der Ecken, J., M. Muller, W. Lehman, D.J. Manstein, P.A. Penczek and S. Raunser. 2015.
Structure of the F-actin-tropomyosin complex. Nature 519: 114–117.
Vo-Dinh, T. 2005. Protein Nanotechnology: Protocols, Instrumentation, and Applications.
Humana Press, Totowa, New Jersey.
Wang, H. and G. Oster. 1998. Energy transduction in the F1 motor of ATP synthase. Nature 396: 279–282.
Wang, Y., D. Zhang, Q. Tan, M.X. Wang and L.Q. Gu. 2011. Nanopore-based detection of circulating microRNAs in lung cancer patients. Nat. Nanotechnol. 6: 668–674.
Weisenberg, R.C. 1972. Microtubule formation in vitro in solutions containing low calcium concentrations. Science 177: 1104–1105.
Whittaker, M., E.M. Wilson-Kubalek, J.E. Smith, L. Faust, R.A. Milligan and H.L. Sweeney.
1995. A 35-Å movement of smooth muscle myosin on ADP release. Nature 378: 748–751.
Wilkens, S., E. Vasilyeva and M. Forgac. 1999. Structure of the vacuolar ATPase by electron microscopy. J. Biol. Chem. 274: 31804–31810.
Wu, H. 2013. Higher-order assemblies in a new paradigm of signal transduction. Cell 153: 1–6.
Wu, X., Z.Y. Yang, Y. Li, C.M. Hogerkorp, W.R. Schief, M.S. Seaman, T. Zhou, S.D. Schmidt, L. Wu, L. Xu, N.S. Longo, K. McKee, S. O’Dell, M.K. Louder, D.L. Wycuff, Y. Feng, M. Nason, N. Doria-Rose, M. Connors, P.D. Kwong, M. Roederer, R.T. Wyatt, G.J. Nabel and J.R. Mascola. 2010. Rational design of envelope identifi es broadly neutralizing human monoclonal antibodies to HIV-1. Science 329: 856–61.
Yager, P., T. Edwards, E. Fu, K. Helton, K. Nelson, M.R. Tam and B.H. Weigl. 2006. Microfl uidic diagnostic technologies for global public health. Nature 442: 412–418.
Yokoi, H., T. Kinoshita and S. Zhang. 2005. Dynamic reassembly of peptide RADA16 nanofi ber scaffold. Proc. Natl. Acad. Sci. USA 102: 8414–8419.
Zhang, X., L. Jin, Q. Fang, W.H. Hui and Z.H. Zhou. 2010. 3.3 Å cryo-EM structure of a nonenveloped virus reveals a priming mechanism for cell entry. Cell 141: 472–482.
Zhao, G., J.R. Perilla, E.L. Yufenyuy, X. Meng, B. Chen, J. Ning, J. Ahn, A.M. Gronenborn, K. Schulten, C. Aiken and P. Zhang. 2013. Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics. Nature 497: 643–646.
Zhao, M., S. Wu, Q. Zhou, S. Vivona, D.J. Cipriano, Y. Cheng and A.T. Brunger. 2015. Mechanistic insights into the recycling machine of the SNARE complex. Nature 518: 61–67.
Zhou, Y., J.H. Morais-Cabral, A. Kaufman and R. MacKinnon. 2001. Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 Å resolution.
Nature 414: 43–38.
4 4
Smart Materials for Controlled Drug Release
Linfeng Chen
ABSTRACT
Smart materials involving in the applications of chemotherapeutics have been increasingly developing for several decades with the advance in materials science and nanotechnology. This chapter presents a comprehensive view of the most promising smart materials for controlled drug release. The contents are divided into three main parts based on the materials, including smart inorganic materials, smart polymer materials, and other emerging nanomaterials. These intelligent materials are designed with fascinating properties, such as biocompatibility, a long circulation time in the bloodstream, imaging, and target recognition. Especially, they could be responsive to internal or external stimulus, such as pH, temperature, light, enzymes, magnetism, and chemicals. The chapter is essential for a wide audience, including undergraduate students, graduate students, PhD students, as well as independent researchers with diverse backgrounds across chemistry, biomedical science, materials sciences, and biotechnology.
Department of Materials Science and Engineering, Technion-Israel Institute of Technology, 32000, Haifa, Israel.
Email: lfchen@tx.technion.ac.il; chlfstorm@gmail.com
1. Introduction
A disease is one of the secret powers, which could cause a disaster to the human civilization, but at the same time promote the fast development of science and technology. As one of the typical diseases, cancers have become a leading cause of death worldwide. According to the International Agency for Research on Cancer, approximately 14.1 million new cases of cancer occurred globally, which caused about 8.2 million deaths in 2012 (Stewart and Wild 2014). Cancer is defi ned as a group of diseases, which are featured by rapid creation of abnormal cells which can grow beyond their boundaries.
In order to solve the problem, various methods including chemotherapy, radiation, surgery, palliative care, and immunotherapy are utilized, which bring serious side-effects, or can not completely defeat the disease. With the development of nanoscience and nanotechnology, controlled drug release (CDR) systems bring new hope for managing the problem.
In a broad sense, CDR refers to the strategies involving the controlling of the release event of drugs or other molecules. Specifi cally, smart materials are one of the critical elements. Smart nanomaterials are defi ned as the materials in the nanoscale size, which are sensitive to stimulus, such as pH, light, temperature, electricity, magnetic fi eld, biomolecules, and enzymes.
The smart nanomaterials applied in CDR could achieve target delivery and release of drugs triggered by the stimulus. By controlling the dose, time, and release site, the pharmacological effects are enhanced and side effects are reduced. Smart nanomaterials are exactly the development of concept
“Magic Bullet” proposed by Ehrlich as early as in 1906 (Strebhardt and Ullrich 2008).
From the fi rst report about the related release of solid to the smart materials studied in CDR, it took more than one hundred years and various kinds of materials have been employed as the formulations for CDR (Fig. 1). The evolution of CDR could be traced back to 1897 when Noyes and Whitney investigated the process of dissolution (Noyes and Whitney 1897).
The breakthroughs happened in 1960s when Folkman designed a silicon rubber device which could prolong the drug release. He also achieved the release of anesthetic agents in rabbits, which was proposed to be as the planted device with controlled release of drugs (Folkman and Long 1964, Folkman et al. 1966). It wasn’t until the 1970s that the nanomaterials were fi rst proposed, followed by the fi rst usage in the clinical in the 1980s. In the 1990s, the fi eld of CDR came into the smart nanomaterials era (Hoffman 2008).
The evolution of CDR is dependent on the engineered materials. During the past decades, the advances of materials science have offered inspiration not only for the modifi cation of materials, but also for numerous possibilities of new materials with potential applications in biomedicine. As the largest
group, polymers have garnered much attention from the beginning, which is going to the present, including hydrogels, capsules, polymersomes, and micelles. In the past couple of decades, inorganic materials have received increasingly interests in the field of CDR, such as mesoporous silica nanomaterials (MSNs), iron oxide nanomaterials (IONMs), and zinc oxide (ZnO). In recent years, some emerging materials are also developed and employed in this fi eld due to their unique properties, e.g., gold nanoparticles (AuNPs), metal-organic frameworks (MOFs), graphene and derivatives, and carbon nanotubes (CNTs). Figure 1 presents an overview of the evolution of CDR based on diverse materials.