Smart Nanomaterials and Their Applications


Smart Nanomaterials and Their Applications

Md. Kawsar Alam, Rejwana Karim, A. J. Saleh Ahammad

Nanomaterials are one of the most amazing creations of human civilization because of their unprecedented potential. These materials are eminent to own excellent electrical, thermal, optical, strong mechanical strength, and catalytic properties. Gadgets or sensors made of nanoparticles are used to determine harmful substances or contaminants of the environment as well as have human biomedical health applications. They have drawn significant attention in the medical sector for possessing remarkable reactivity, extraordinary molar-extinction coefficient, specificity, long-lasting stability, and stronger absorption. In the case of certain biomedical utilization, the fabricating of nanoparticles is problematic because they lack adequate functional characteristics. Smart nanomaterials grab this attention significantly since they can be triggered by external elements like temperature, pH, light, pressure, enzyme, etc. This chapter intends to provide the classifications and applications of smart nanomaterials as tissue engineering, drug delivery, sensor, etc.

Smart Nanomaterials, Tissue Engineering, Drug Delivery, Sensors

Published online 11/15/2022, 25 pages

Citation: Md. Kawsar Alam, Rejwana Karim, A. J. Saleh Ahammad, Smart Nanomaterials and Their Applications, Materials Research Foundations, Vol. 135, pp 100-124, 2023


Part of the book on Emerging Nanomaterials and Their Impact on Society in the 21st Century

[1] S. Amador-Vargas, M. Dominguez, G. León, B. Maldonado, J. Murillo, G.L. Vides, Leaf-folding response of a sensitive plant shows context-dependent behavioral plasticity, Plant Ecol. 215 (2014) 1445-1454.
[2] E. Reyssat, L. Mahadevan, Hygromorphs: From pine cones to biomimetic bilayers, J. R. Soc. Interface 6 (2009) 951-957.
[3] R. Elbaum, L. Zaltzman, I. Burgert, P. Fratzl, The role of wheat awns in the seed dispersal unit, Science 316 (2007) 884-886.
[4] R.M. Erb, J.S. Sander, R. Grisch, A.R. Studart, Self-shaping composites with programmable bioinspired microstructures. Nat. Commun. 4 (2013) 1712.
[5] Y. Forterre, J.M. Skotheim, J. Dumais, L. Mahadevan, How the Venus flytrap snaps, Nature 433 (2005) 421-425.
[6] T. Takagi, A concept of intelligent materials, J. Intell. Mater. Syst. Struct. 1 (1990) 149-156.
[7] Y. Lu, W. Sun, Z. Gu, Stimuli-responsive nanomaterials for therapeutic protein delivery, J. Control. Release 194 (2014) 1-19.
[8] S. Kim, S.H. Ku, S.Y. Lim, J.H. Kim, C.B. Park, Graphene-biomineral hybrid materials, Adv. Mater. 23 (2011) 2009-2014.
[9] T.F. Otero, J.G. Martinez, J. Arias-Pardilla, Biomimetic electrochemistry from conducting polymers. A review: Artificial muscles, smart membranes, smart drug delivery and computer/neuron interfaces, Electrochim. Acta 84 (2012) 112-128.
[10] D. Bitounis, H. Ali-Boucetta, B.H. Hong, D.H. Min, K. Kostarelos, Prospects and challenges of graphene in biomedical applications, Adv. Mater. 25 (2013) 2258-2268.
[11] L. Liu, P. Li, G. Zhou, M. Wang, X. Jia, M. Liu, X. Niu, W. Song, H. Liu, Y. Fan, Increased proliferation and differentiation of pre-osteoblasts MC3T3-E1 cells on nanostructured polypyrrole membrane under combined electrical and mechanical stimulation, J. Biomed. Nanotechnol. 9 (2013) 1532-1539.
[11] G. Aragay, F. Pino, A. Merkoçi, Nanomaterials for sensing and destroying pesticides, Chem. Rev. 112 (2012) 5317-5338.
[12] M.R. Willner, P.J. Vikesl, Nanomaterial enabled sensors for environmental contaminants, J. Nanobiotechnol. 16 (2018) 95.
[13] J. Zhang, L. Wang, D. Pan, S. Song, F.Y.C. Boey, H. Zhang, C. Fan, Visual cocaine detection with gold nanoparticles and rationally engineered aptamer structures, Small 4 (2008) 1196-1200.
[14] S. Song, Z. Liang, J. Zhang, L. Wang, G. Li, C. Fan, Gold-nanoparticle-based multicolor nanobeacons for sequence-specific DNA analysis, Angew. Chem. Int. Ed. Engl. 48 (2009) 8670-8674.
[15] P. B. Chouke, K. M. Dadure, A. K. Potbhare, G. S. Bhusari, A. Mondal, K. Chaudhary, V. Singh, M. F. Desimone, R. G. Chaudhary, D. T. Masram, Biosynthesized δ-Bi2O3 nanoparticles from Crinum viviparum flower extract for photocatalytic dye degradation and molecular docking, ACS Omega, 7 (2022) 20983-20993.
[17] P.B. Chouke, A.K. Potbhare, N.P. Meshram, M. M. Rai, K.M. Dadure, K. Chaudhary, A.R. Rai, M. Desimone, R. G. Chaudhary, D.T. Masram, Bioinspired NiO nanospheres: Exploring in-vitro toxicity using Bm-17 and L. rohita liver cells, DNA degradation, docking and proposed vacuolization mechanism. ACS Omega. 7 (2022) 6869−6884.
[18] S.S. Das, P. Bharadwaj, M. Bilal, M. Barani, A. Rahdar, P. Taboada, S. Bungau, G.Z. Kyzas, Stimuli-responsive polymeric nanocarriers for drug delivery, imaging, and theragnosis, Polymers 12 (2020) 1397.
[19] A K. Potbhare, R.G. Chaudhary, P.B. Chouke, A. Rai, A. Abdala, R. Mishra, M. Desimone, Graphene-based materials and their nanocomposites with metal oxides: Biosynthesis, electrochemical, photocatalytic and antimicrobial applications. Mater. Res. Forum. 83 (2020) 79-116.
[20] M. Pinteala, M.J.M. Abadie, R.D. Rusu, Smart Supra- and Macro-Molecular Tools for Biomedical Applications, Materials 13 (2020) 3343.
[21] E. Cabane, X. Zhang, K. Langowska, C.G. Palivan, W. Meier, Stimuli-responsive polymers and their applications in nanomedicine, Biointerphases 7 (2012) 9.
[22] P.J. Flory, Thermodynamics of high polymer solutions, J. Chem. Phys. 9 (1941) 660.
[23] M.L. Huggins, Some properties of solutions of long-chain compounds, J. Phys. Chem. 46 (1942) 151-158.
[24] D. Roy, W.L.A. Brooks, B. S. Sumerlin, New directions in thermoresponsive polymers, Chem. Soc. Rev.42 (2013) 7214-7243.
[25] S. Glatzel, A. Laschewsky and J.F. Lutz, Well-defined uncharged polymers with a sharp UCST in water and in physiological milieu, Macromolecules 44 (2011) 413-415.
[26] J. Seuring and S. Agarwal, First example of a universal and cost-effectiveapproach: Polymers with tunable upper critical solution temperature in water and electrolyte solution, Macromolecules 45 (2012) 3910-3918.
[27] Q. Liu, H. Yu, Q. Zhang, D. Wang, X. Wang, Temperature-Responsive Self-Assembly of Single Polyoxometalates Clusters Driven by Hydrogen Bonds, Adv. Funct. Mater. 31 (2021) 2103561.
[28] M. Zhu, X.Z. Song, S.Y. Song, S.N. Zhao, X. Meng, L.L Wu, C. Wang, H.J. Zhang, A Temperature‐Responsive Smart Europium Metal‐Organic Framework Switch for Reversible Capture and Release of Intrinsic Eu3+ Ions, Adv. Sci. 2 (2015) 1500012.
[29] M.G. Arafa, R.F. El-Kased, M.M. Elmazar, Thermoresponsive gels containing gold nanoparticles as smart antibacterial and wound healing agents, Sci. Rep. 8 (2018) 13674.
[30] Y. Chen, Y. Gao, L.P. da Silva, R.P. Pirraco, M. Ma, L. Yang, R.L. Reis, J. Chen, A thermo-/pH-responsive hydrogel (PNIPAM-PDMA-PAA) with diverse nanostructures and gel behaviors as a general drug carrier for drug release, Polym. Chem. 9 (2018) 4063-4072.
[31] M.R. Abidian, D.H. Kim, D.C. Martin, Conducting-Polymer Nanotubes for Controlled Drug Release, Adv. Mater. 18 (2006) 405-409.
[32] N. Royo-Gascon, M. Wininger, J.I. Scheinbeim, B.L. Firestein, W. Craelius, Piezoelectric substrates promote neurite growth in rat spinal cord neurons, Ann. Biomed. Eng. 41 (2013) 112-122.
[33] R.F. Valentini, T.G. Vargo, J.A. Gardella Jr., P. Aebischer, Electrically charged polymeric substrates enhance nerve fibre outgrowth In vitro, Biomaterials 13 (1992) 183-190.
[34] P. Aebischer, R.F. Valentini, P. Dario, C. Domenici, P.M. Galletti, Piezoelectric guidance channels enhance regeneration in the mouse sciatic nerve after axotomy, Brain Res. 436 (1987) 165-168.
[35] H. Delaviz, A. Faghihi, A.A. Delshad, M. hadiBahadori, J. Mohamadi, A. Roozbehi, Repair of peripheral nerve defects using a polyvinylidene fluoride channel containing nerve growth factor and collagen gel in adult rats, Cell J. 13 (2011) 137-142.
[36] F. Yang, R. Murugan, S. Wang, S. Ramakrishna, Electrospinning of nano/micro scale poly(L-lactic acid) aligned fibers and their potential in neural tissue engineering, Biomaterials 26 (2005) 2603-2610.
[37] R.C. de Guzman, J.A. Loeb, P.J. VandeVord, Electrospinning of matrigel to deposit a basal lamina-like nanofiber surface, J. Biomater. Sci. Polym. Ed. 21 (2010) 1081-1101.
[38] T.J. O’Shaughnessy, H.J. Lin, W. Ma, Functional synapse formation among rat cortical neurons grown on three-dimensional collagen gels, Neurosci. Lett. 340 (2003) 169-172.
[39] M.K. Hossain, H. Minami, S.M. Hoque, M.M. Rahman, M.K. Sharafat, M.F. Begum, M.E. Islam, H. Ahmad, Mesoporous electromagnetic composite particles: Electric current responsive release of biologically active molecules and antibacterial properties, Colloids Surf. B: Biointerfaces 181 (2019) 85-93.
[40] K.J. Otto, C.E. Schmidt, Neuron-targeted electrical modulation, Science 367 (2020) 1303-1304.
[41] Z. Liu, S. Zhang, Y.M. Jin, H. Ouyang, Y. Zou, X.X. Wang, L.X. Xie, Z.J. Li, Flexible piezoelectric nanogenerator in wearable self-powered active sensor for respiration and healthcare monitoring, Semicond. Sci. Technol. 32 (2017) 064004.
[42] S. Moreno, M. Baniasadi, S. Mohammed, I. Mejia, Y. Chen, M.A. Quevedo-Lopez, N. Kumar,S. Dimitrijevich, M. Minary-Jolandan, Biocompatible collagen films as substrates for flexible implantable electronics, Adv. Electron. Mater. 1 (2015) 1500154.
[43] W. Han, H. He, L. Zhang, C. Dong, H. Zeng, Y. Dai, L. Xing, Y. Zhang, X. Xue, A Self-Powered Wearable Non-invasive Electronic-Skin for Perspiration Analysis Basing on Piezo-Biosensing Unit Matrix of Enzyme/ZnO Nanoarrays, ACS Appl. Mater. Interfaces 9 (2017) 29526-29537.
[44] J. Park, M. Kim, Y. Lee, H.S. Lee, H. Ko, Fingertip skin-inspired microstructured ferroelectric skins discriminate static/dynamic pressure and temperature stimuli, Sci. Adv. 1 (2015) e1500661.
[45] Y.Y. Chen, H.T. Chang, Y.C. Shiang, Y.L. Hung, C.K. Chiang, C.C. Huang, Colorimetric assay for lead ions based on the leaching of gold nanoparticles, Anal. Chem. 81 (2009) 9433-9439.
[46] Y.F. Lee, F.H. Nan, M.J. Chen, H.Y. Wu, C.W. Ho, Y.Y. Chen, C.C. Huang,Detection and removal of mercury and lead ions by using gold nanoparticle-based gel membrane, Anal Methods. 4 (2012) 1709-1717.
[47] C.N. Lok, C.M. Ho, R. Chen, Q.Y. He, W.Y. Yu, H. Sun, P.K.H. Tam, J.F. Chiu, C.M. Che, Silver nanoparticles: partial oxidation and antibacterial activities, J. Biol. Inorg. Chem. 12 (2007) 527-534.
[48] H. Fan, Y. Li, D. Wu, H. Ma, K. Mao, D. Fan, B. Du, H. Li, Q. Wei,Electrochemical bisphenol A sensor based on N-doped graphene sheets, Anal. Chim. Acta. 711 (2012) 24-28.
[49] J. Dong, X. Fan, F. Qiao, S. Ai, H. Xin, A novel protocol for ultra-trace detection of pesticides: Combined electrochemical reduction of Ellman’s reagent with acetylcholinesterase inhibition, Anal. Chim. Acta 761 (2013) 78-83.
[50] O. Perlman, H. Azhari, MRI and ultrasound imaging of nanoparticles for medical diagnosis, in: C. Kumar CSSR (edS) Nanotechnology characterization tools for biosensing and medical diagnosis, Springer, Berlin, Heidelberg, 2018, pp. 333-365.
[51] Y. Shen, F.L. Goerner, C. Snyder, J.N. Morelli, D. Hao, D. Hu, X. Li, V.M. Runge, T1 relaxivities of gadolinium-based magnetic resonance contrast agents in human whole blood at 1.5, 3, and 7 T, Investig. Radiol. 50 (2015) 330-338.
[52] R. Klajn, Spiropyran-based dynamic materials, Chem. Soc. Rev. 43 (2014) 148-184.
[53] Q. Zhang, C. Weber, U.S. Schubert, R. Hoogenboom, Thermoresponsive polymers with lower critical solution temperature: from fundamental aspects and measuring techniques to recommended turbidimetry conditions, Mater. Horizons 4 (2017) 109-116.
[54] G. Marcelo, L.R. Areias, M.T. Viciosa, J.M.G. Martinho, J.P.S. Farinha, PNIPAm-based microgels with a UCST response, Polymer 116 (2017) 261-267.
[55] F.F. Sahle, M. Gulfam, T.L. Lowe, Design strategies for physical-stimuli-responsive programmable nanotherapeutics, Drug Discov. Today 23 (2018) 992-1006.
[56] L.J. Jeanneret, The targeted delivery of cancer drugs across the blood-brain barrier: chemical modifications of drugs or drug-nanoparticles?, Drug Discov. Today 13 (2008) 1099-1106.
[57] H. Sun, M. Feng, S. Chen, R. Wang, Y. Luo, B. Yin, J. Li, X. Wang, Near-infrared photothermal liposomal nanoantagonists for amplified cancer photodynamic therapy, J. Mater. Chem. B 8 (2020) 7149-7159.
[58] P. Zhao, M. Ni, C. Chen, Z. Zhou, X. Li, C. Li, Y.Xie, J. Fei, Stimuli-enabled switch-like paracetamol electrochemical sensor based on thermosensitive polymer and MWCNTs-GQDs composite nanomaterial, Nanoscale11 (2019) 7394-7403.
[59] Y. Liu, T. Shen, L. Hu, H. Gong, C. Chen, X. Chen, Development of athermosensitive molecularly imprinted polymer resonance light scattering sensor for rapid and highly selective detection of hepatitis A virus in vitro, Sens.Actuators B Chem. 253 (2017) 1188-93.
[60] W. P. Mason, Piezoelectricity, its history and applications, J. Acoust. Soc. Am. 70 (1981) 1561-1566.
[61] S. Chandrasekaran, C. Bowen, J. Roscow, Y. Zhang, D.K. Dang, E.J. Kim, R.D.K. Misra, L. Deng, J.S. Chung, S.H. Hur, Micro-scale to nano-scale generators for energy harvesting: Self powered piezoelectric, triboelectric and hybrid devices, Phys. Rep. 792 (2018) 1-33.
[62] V.Y. Topolov, C.R. Bowen, P. Bisegna, New aspect-ratio effect in three-component composites for piezoelectric sensor, hydrophone and energy-harvesting applications, Sens. Actuators A Phys. 229 (2015) 94-103.
[63] D. Grieshaber, R. MacKenzie, J. Vörös, E. Reimhult, Electrochemical biosensors-sensor principles and architectures, Sensors 8 (2008) 1400-58.
[64] O.A. Sadik, A.O. Aluoch, A. Zhou, Status of biomolecular recognition using electrochemical techniques, Biosens. Bioelectron. 24 (2009) 2749-2765.
[65] S. Link, M.A. El-Sayed, Spectral properties and relaxation dynamics of surface plasmon electronic oscillations in gold and silver nanodots and nanorods, J. Phys. Chem. B 103 (1999) 8410-8426.
[66] K. Saha, S.S. Agasti, C. Kim, X. Li, V.M. Rotello Gold nanoparticles in chemical and biological sensing, Chem. Rev. 112 (2012) 2739-2779.
[67] W. Yang, K.R. Ratinac, S.P. Ringer, P. Thordarson, J.J Gooding, F. Braet, Carbon nanomaterials in biosensors: should you use nanotubes or graphene?, Angew. Chem. Int. Ed. Engl. 49 (2010) 2114-2138.
[68] J.H. Ha, H.H. Shin, H.W. Choi, J.H. Lim, S.J. Mo, C.D. Ahrberg, J.M. Lee, B.G. Chung, Electro-responsive hydrogel-based microfluidic actuator platform for photothermal therapy, Lab Chip 20 (2020) 3354-3364.
[69] N.H. Nassab, D. Samanta, Y. Abdolazimi, J.P. Annes, R.N. Zare, Electrically controlled release of insulin using polypyrrole nanoparticles, Nanoscale 9 (2017) 143-149.
[70] V.F. Cardoso, A. Francesko, C. Ribeiro, M. Bañobre‐López, P. Martins, S. Lanceros‐Mendez, Advances in magnetic nanoparticles for biomedical applications, Adv. Healthc. Mater. 7 (2018) 1700845.
[71] K. Mahmoudi, A. Bouras, D. Bozec, R. Ivkov, C. Hadjipanayis, Magnetic hyperthermia therapy for the treatment of glioblastoma: a review of the therapy’s history, efficacy and application in humans, Int. J. Hyperth. 34 (2018) 1316-1328.
[72] H. Wei, S.M.H. Abtahi, P.J. Vikesland, Plasmonic colorimetric and SERS sensors for environmental analysis, Environ. Sci.: Nano 2 (2015) 120-135.
[73] E. Morales‐Narváez, L. Baptista‐Pires, A. Zamora‐Gálvez, A. Merkoçi, Graphene-Based Biosensors: Going Simple, Adv. Mater. 29 (2017) 1604905.
[74] M. Lan, S. Zhao, W. Liu, C.S. Lee, W. Zhang, P. Wang, Photosensitizers for photodynamic therapy, Adv. Healthc. Mater. 8 (2019) 1900132.
[75] R. Vankayala, K.C. Hwang, Near‐infrared‐light‐activatable nanomaterial‐mediated phototheranostic nanomedicines: an emerging paradigm for cancer treatment, Adv. Mater. 30 (2018) 1706320.
[76] A.A. Date, J. Hanes, L.M. Ensign, Nanoparticles for oral delivery: Design, evaluation and state-of-the-art, J. Control. Release 240 (2016) 504-526.
[77] A. Waugh, A. Grant, Anatomy and Physiology in Health and Illness, tenth ed., Philadelphia, Pa, USA: Churchill Livingstone, Elsevier, 2007.
[78] O. Hoegh-Guldberg, P.J. Mumby, A.J. Hooten, R.S. Steneck, P. Greenfield, E. Gomez, C.D. Harvell, P.F. Sale, A.J. Edwards, K. Caldeira, N. Knowlton, Coral reefs under rapid climate change and ocean acidification, Science 318 (2007) 1737-1742.
[79] X. Xie, T.C. Sun, J. Xue, Z. Miao, X. Yan, W. Fang, Q. Li, R. Tang, Y. Lu, L. Tang, Z. Zha, Ag nanoparticles cluster with pH‐triggered reassembly in targeting anti-microbial applications, Adv. Funct. Mater. 30 (2020) 2000511.
[80] Y. Wang, C. Wang, Y. Li, G. Huang, T. Zhao, X. Ma, Z. Wang, B.D. Sumer, M.A. White, J. Gao, Digitization of Endocytic pH by Hybrid Ultra‐pH‐Sensitive Nanoprobes at Single‐Organelle Resolution, Adv. Mater. 29 (2017) 1603794.
[81] P.A. Lund, D.D. Biase, O. Liran, O. Scheler, N.P. Mira, Z. Cetecioglu, E.N. Fernandez, S. Bover-Cid, R. Hall, M. Sauer, C. O’Byrne, Understanding how microorganisms respond to acid pH is central to their control and successful exploitation, Front. Microbiol. 11 (2020) 556140.
[82] M.R. Aguilar, J.S. Román, 1 – Introduction to smart polymers and their applications, in: M.R. Aguilar, J.S. Román (Eds.), Smart Polymers and Their Applications, Woodhead Publishing, Cambridge, UK, 2014, pp. 1-11
[83] F. Reyes-Ortega, 3 – pH-responsive polymers: properties, synthesis and applications, in: M.R. Aguilar, J.S. Román (Eds.), Smart Polymers and Their Applications, Woodhead Publishing, Cambridge, UK, 2014, pp. 45-92.
[84] B. Sultankulov, D. Berillo, K. Sultankulova, T. Tokay, A. Saparov, Progress in the Development of Chitosan-Based Biomaterials for Tissue Engineering and Regenerative Medicine, Biomol. 9 (2019) 470.
[85] L. Yan , S.H. Crayton , J.P. Thawani , A. Amirshaghaghi ,A.Tsourkas , Z. Cheng, A pH-Responsive Drug-Delivery Platform Based on Glycol Chitosan-CoatedLiposomes, Small 11 (2015) 4870-4874.
[86] L. Yan, S.H. Crayton, J.P. Thawani, A. Amirshaghaghi, A. Tsourkas, Z. Cheng, A pH‐Responsive Drug‐Delivery Platform Based on Glycol Chitosan-Coated Liposomes, Small 11 (2015) 4870-4874.
[87] A.F. Radovic-Moreno, T.K. Lu, V.A. Puscasu, C.J. Yoon, R. Langer, O.C. Farokhzad, Surface charge-switching polymeric nanoparticles for bacterial cell wall-targeted delivery of antibiotics, ACS Nano 6 (2012) 4279-4287.
[88] Y. Kang, W. Ha, Y.Q. Liu, Y. Ma, M.M. Fan, L.S. Ding, S. Zhang, B.J. Li, pH-responsive polymer-drug conjugates as multifunctional micelles for cancer-drug delivery, Nanotechnology 25 (2014) 335101.
[89] R. Tomlinson, J. Heller, S. Brocchini, R. Duncan, Polyacetal− doxorubicin conjugates designed for pH-dependent degradation, Bioconjug. Chem. 2003, 14, 1096-1106.
[90] W. Wang, G. Liang, W. Zhang, D. Xing, X. Hu, Cascade-Promoted Photo-Chemotherapy against Resistant Cancers by Enzyme-Responsive Polyprodrug Nanoplatforms, Chem. Mater. 30 (2018) 3486-3498.
[91] J.J. Hu, L.H. Liu, Z.Y. Li, R.X. Zhuo, X.Z. Zhang, MMP-responsive theranostic nanoplatform based on mesoporous silica nanoparticles for tumor imaging and targeted drug delivery. J. Mater. Chem. B 4 (2016) 1932-1940.
[92] Y. Ding, Y. Hao, Z. Yuan, B. Tao, M. Chen, C. Lin, P. Liu, K. Caib, A dual-functional implant with an enzyme-responsive effect for bacterial infection therapy and tissue regeneration, Biomater. Sci. 8 (2020) 1840-1854.
[93] L.P. Datta, A. Chatterjee, K. Acharya, P. De, M. Das, Enzyme responsive nucleotide functionalized silver nanoparticles with effective anti-microbial and anticancer activity, New J. Chem. 41 (2017) 1538-1548.
[94] S.T. Gunawan, K. Kempe, T. Bonnard, J. Cui, K. Alt, L.S. Law, X. Wang, E. Westein, G.K. Such, K. Peter, C.E. Hagemeyer, F. Caruso, Multifunctional Thrombin-Activatable Polymer Capsules for Specific Targeting to Activated Platelets, Adv. Mater. 27 (2015) 5153-5157.