Abstract
An emerging focus in nanomedicine is the exploration of multifunctional nanocomposite materials that integrate stimuli-responsive, therapeutic, and/or diagnostic functions. In this effort, cysteine-rich proteins have drawn considerable attention as a versatile platform due to their good biodegradability, biocompatibility, and ease of chemical modification. This review surveys cysteine-rich protein-based biomedical materials, including protein-metal nanohybrids, gold nanoparticle-protein agglomerates, protein-based nanoparticles, and hydrogels, with an emphasis on their preparation methods, especially those based on the cysteine residue-related reactions. Their applications in tumor-targeted drug delivery and diagnostics are highlighted.
Keywords: Cysteine-rich protein, drug delivery, cancer diagnostics, protein-based nanoparticle, hydrogel, biomedical material.
[1]
Lu, Y.; Aimetti, A.A.; Langer, R.; Gu, Z. Bioresponsive materials. Nat. Rev. Mater., 2016, 1, 16075.
[3]
Mitragotri, S.; Burke, P.A.; Langer, R. Overcoming the challenges in administering biopharmaceuticals: Formulation and delivery strategies. Nat. Rev. Drug Discov., 2014, 13(9), 655-672.
[4]
Chow, E.K.; Zhang, X.Q.; Chen, M.; Lam, R.; Robinson, E.; Huang, H.; Schaffer, D.; Osawa, E.; Goga, A.; Ho, D. Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment. Sci. Transl. Med., 2011, 3(73), 73ra21.
[5]
Cabral, H.; Kataoka, K. Progress of drug-loaded polymeric micelles into clinical studies. J. Control. Release, 2014, 190, 465-476.
[6]
Kim, H.J.; Kim, A.; Miyata, K.; Kataoka, K. Recent progress in development of siRNA delivery vehicles for cancer therapy. Adv. Drug Deliv. Rev., 2016, 104, 61-77.
[7]
Muthu, M.S.; Leong, D.T.; Mei, L.; Feng, S.S. Nanotheranostics - application and further development of nanomedicine strategies for advanced theranostics. Theranostics, 2014, 4(6), 660-677.
[8]
Shi, J.; Kantoff, P.W.; Wooster, R.; Farokhzad, O.C. Cancer nanomedicine: Progress, challenges and opportunities. Nat. Rev. Cancer, 2017, 17(1), 20-37.
[9]
Caldorera-Moore, M.E.; Liechty, W.B.; Peppas, N.A. Responsive theranostic systems: integration of diagnostic imaging agents and responsive controlled release drug delivery carriers. Acc. Chem. Res., 2011, 44(10), 1061-1070.
[10]
Vermonden, T.; Censi, R.; Hennink, W.E. Hydrogels for protein delivery. Chem. Rev., 2012, 112(5), 2853-2888.
[11]
Censi, R.; Di Martino, P.; Vermonden, T.; Hennink, W.E. Hydrogels for protein delivery in tissue engineering. J. Control. Release, 2012, 161(2), 680-692.
[12]
Maham, A.; Tang, Z.; Wu, H.; Wang, J.; Lin, Y. Protein-based nanomedicine platforms for drug delivery. Small, 2009, 5(15), 1706-1721.
[13]
Pan, U.N.; Khandelia, R.; Sanpui, P.; Das, S.; Paul, A.; Chattopadhyay, A. Protein-based multifunctional nanocarriers for imaging, photothermal therapy, and anticancer drug delivery. ACS Appl. Mater. Interfaces, 2016.
[14]
Chalker, J.M.; Bernardes, G.J.; Davis, B.G.A. “tag-and-modify” approach to site-selective protein modification. Acc. Chem. Res., 2011, 44(9), 730-741.
[15]
Boutureira, O.; Bernardes, G.J. Advances in chemical protein modification. Chem. Rev., 2015, 115(5), 2174-2195.
[16]
Krall, N.; da Cruz, F.P.; Boutureira, O.; Bernardes, G.J. Site-selective protein-modification chemistry for basic biology and drug development. Nat. Chem., 2016, 8(2), 103-113.
[17]
Algar, W.R.; Prasuhn, D.E.; Stewart, M.H.; Jennings, T.L.; Blanco-Canosa, J.B.; Dawson, P.E.; Medintz, I.L. The controlled display of biomolecules on nanoparticles: a challenge suited to bioorthogonal chemistry. Bioconjug. Chem., 2011, 22(5), 825-858.
[18]
Elzoghby, A.O.; Samy, W.M.; Elgindy, N.A. Albumin-based nanoparticles as potential controlled release drug delivery systems. J. Control. Release, 2012, 157(2), 168-182.
[19]
Elsadek, B.; Kratz, F. Impact of albumin on drug delivery-new applications on the horizon. J. Control. Release, 2012, 157(1), 4-28.
[20]
Elzoghby, A.O. Gelatin-based nanoparticles as drug and gene delivery systems: reviewing three decades of research. J. Control. Release, 2013, 172(3), 1075-1091.
[21]
Kratz, F.; Elsadek, B. Clinical impact of serum proteins on drug delivery. J. Control. Release, 2012, 161(2), 429-445.
[22]
An, B.; Lin, Y.S.; Brodsky, B. Collagen interactions: Drug design and delivery. Adv. Drug Deliv. Rev., 2016, 97, 69-84.
[23]
Elzoghby, A.O.; Samy, W.M.; Elgindy, N.A. Protein-based nanocarriers as promising drug and gene delivery systems. J. Control. Release, 2012, 161(1), 38-49.
[24]
Kratz, F. A clinical update of using albumin as a drug vehicle - a commentary. J. Control. Release, 2014, 190, 331-336.
[25]
Lu, Y.; Mo, R.; Tai, W.; Sun, W.; Pacardo, D.B.; Qian, C.; Shen, Q.; Ligler, F.S.; Gu, Z. Self-folded redox/acid dual-responsive nanocarriers for anticancer drug delivery. Chem. Commun. (Camb.), 2014, 50(95), 15105-15108.
[26]
Zhao, M.; Biswas, A.; Hu, B.; Joo, K.I.; Wang, P.; Gu, Z.; Tang, Y. Redox-responsive nanocapsules for intracellular protein delivery. Biomaterials, 2011, 32(22), 5223-5230.
[27]
Roy, S.; Palui, G.; Banerjee, A. The as-prepared gold cluster-based fluorescent sensor for the selective detection of As(III) ions in aqueous solution. Nanoscale, 2012, 4(8), 2734-2740.
[28]
Roy, S.; Baral, A.; Bhattacharjee, R.; Jana, B.; Datta, A.; Ghosh, S.; Banerjee, A. Preparation of multi-coloured different sized fluorescent gold clusters from blue to NIR, structural analysis of the blue emitting Au7 cluster, and cell-imaging by the NIR gold cluster. Nanoscale, 2015, 7(5), 1912-1920.
[29]
Devarie-Baez, N.O.; Silva Lopez, E.I.; Furdui, C.M. Biological chemistry and functionality of protein sulfenic acids and related thiol modifications. Free Radic. Res., 2016, 50(2), 172-194.
[30]
Hoyle, C.E.; Bowman, C.N. Thiol-ene click chemistry. Angew. Chem. Int. Ed. Engl., 2010, 49(9), 1540-1573.
[31]
Wu, D.C.; Loh, X.J.; Wu, Y.L.; Lay, C.L.; Liu, Y. ‘Living’ controlled in situ gelling systems: thiol-disulfide exchange method toward tailor-made biodegradable hydrogels. J. Am. Chem. Soc., 2010, 132(43), 15140-15143.
[32]
Cai, H.; Yao, P. In situ preparation of gold nanoparticle-loaded lysozyme-dextran nanogels and applications for cell imaging and drug delivery. Nanoscale, 2013, 5(7), 2892-2900.
[33]
Liu, J.M.; Chen, J.T.; Yan, X.P. Near infrared fluorescent trypsin stabilized gold nanoclusters as surface plasmon enhanced energy transfer biosensor and in vivo cancer imaging bioprobe. Anal. Chem., 2013, 85(6), 3238-3245.
[34]
Zhao, T.; He, X.W.; Li, W.Y.; Zhang, Y.K. Transferrin-directed preparation of red-emitting copper nanoclusters for targeted imaging of transferrin receptor over-expressed cancer cells. J. Mater. Chem. B Mater. Biol. Med., 2015, 3(11), 2388-2394.
[35]
Lee, H.; Noh, K.; Lee, S.C.; Kwon, I.K.; Han, D.W.; Lee, I.S.; Hwang, Y.S. Human hair keratin and its-based biomaterials for biomedical applications. Tissue Eng. Regen. Med., 2014, 11(4), 255-265.
[36]
Hill, P.; Brantley, H.; Van Dyke, M. Some properties of keratin biomaterials: kerateines. Biomaterials, 2010, 31(4), 585-593.
[37]
Rouse, J.G.; Van Dyke, M.E. A review of keratin-based biomaterials for biomedical applications. Materials (Basel), 2010, 3(2), 999-1014.
[38]
Hill, P.; Brantley, H.; Van Dyke, M. Some properties of keratin biomaterials: kerateines. Biomaterials, 2010, 31(4), 585-593.
[39]
Dykman, L.A.; Khlebtsov, N.G. Multifunctional gold-based nanocomposites for theranostics. Biomaterials, 2016, 108, 13-34.
[40]
Li, Y.; Li, P.; Zhu, R.; Luo, C.; Li, H.; Hu, S.; Nie, Z.; Huang, Y.; Yao, S. Multifunctional gold nanoclusters-based nanosurface energy transfer probe for real-time monitoring of cell apoptosis and self-evaluating of pro-apoptotic theranostics. Anal. Chem., 2016, 88(22), 11184-11192.
[41]
Yang, W.; Guo, W.; Chang, J.; Zhang, B. Protein/peptide-templated biomimetic synthesis of inorganic nanoparticles for biomedical applications. J. Mater. Chem. B Mater. Biol. Med., 2017.
[42]
Xie, J.; Zheng, Y.; Ying, J.Y. Protein-directed synthesis of highly fluorescent gold nanoclusters. J. Am. Chem. Soc., 2009, 131(3), 888-889.
[43]
Le Guével, X.; Hötzer, B.; Jung, G.; Hollemeyer, K.; Trouillet, V.; Schneider, M. Formation of fluorescent metal (Au, Ag) nanoclusters capped in bovine serum albumin followed by fluorescence and spectroscopy. J. Phys. Chem. C, 2011, 115(22), 10955-10963.
[44]
Chaudhari, K.; Xavier, P.L.; Pradeep, T. Understanding the evolution of luminescent gold quantum clusters in protein templates. ACS Nano, 2011, 5(11), 8816-8827.
[45]
Mohanty, J.S.; Baksi, A.; Lee, H.; Pradeep, T. Noble metal clusters protected with mixed proteins exhibit intense photoluminescence. RSC Advances, 2015, 5(59), 48039-48045.
[46]
Baksi, A.; Xavier, P.L.; Chaudhari, K.; Goswami, N.; Pal, S.K.; Pradeep, T. Protein-encapsulated gold cluster aggregates: the case of lysozyme. Nanoscale, 2013, 5(5), 2009-2016.
[47]
Shi, H.; Ou, M.Y.; Cao, J.P.; Chen, G.F. Synthesis of ovalbumin-stabilized highly fluorescent gold nanoclusters and their application as an Hg2+ sensor. RSC Advances, 2015, 5(105), 86740-86745.
[48]
Chattoraj, S.; Bhattacharyya, K. Fluorescent gold nanocluster inside a live breast cell: etching and higher uptake in cancer cell. J. Phys. Chem. C, 2014, 118(38), 22339-22346.
[49]
Yarramala, D.S.; Doshi, S.; Rao, C.P. Green synthesis, characterization and anticancer activity of luminescent gold nanoparticles capped with apo-α-lactalbumin. RSC Advances, 2015, 5(41), 32761-32767.
[50]
Wang, Y.; Yang, T.; Ke, H.; Zhu, A.; Wang, Y.; Wang, J.; Shen, J.; Liu, G.; Chen, C.; Zhao, Y.; Chen, H. Smart albumin-biomineralized nanocomposites for multimodal imaging and photothermal tumor ablation. Adv. Mater., 2015, 27(26), 3874-3882.
[51]
Yang, T.; Wang, Y.; Ke, H.; Wang, Q.; Lv, X.; Wu, H.; Tang, Y.; Yang, X.; Chen, C.; Zhao, Y.; Chen, H. Protein-nanoreactor-assisted synthesis of semiconductor nanocrystals for efficient cancer theranostics. Adv. Mater., 2016, 28(28), 5923-5930.
[52]
Webb, J.A.; Bardhan, R. Emerging advances in nanomedicine with engineered gold nanostructures. Nanoscale, 2014, 6(5), 2502-2530.
[53]
Pacardo, D.B.; Neupane, B.; Rikard, S.M.; Lu, Y.; Mo, R.; Mishra, S.R.; Tracy, J.B.; Wang, G.; Ligler, F.S.; Gu, Z. A dual wavelength-activatable gold nanorod complex for synergistic cancer treatment. Nanoscale, 2015, 7(28), 12096-12103.
[54]
Lin, J.; Zhang, M.G.; Tang, Y.; Wen, B.; Hu, H.; Song, J.; Liu, Y.; Huang, P.; Chen, X. Temporal-spatially transformed synthesis and formation mechanism of gold bellflowers. Nanoscale, 2016, 8(14), 7430-7434.
[55]
Zhang, D.; Neumann, O.; Wang, H.; Yuwono, V.M.; Barhoumi, A.; Perham, M.; Hartgerink, J.D.; Wittung-Stafshede, P.; Halas, N.J. Gold nanoparticles can induce the formation of protein-based aggregates at physiological pH. Nano Lett., 2009, 9(2), 666-671.
[56]
Kah, J.C.; Chen, J.; Zubieta, A.; Hamad-Schifferli, K. Exploiting the protein corona around gold nanorods for loading and triggered release. ACS Nano, 2012, 6(8), 6730-6740.
[57]
Khandelia, R.; Jaiswal, A.; Ghosh, S.S.; Chattopadhyay, A. Gold nanoparticle-protein agglomerates as versatile nanocarriers for drug delivery. Small, 2013, 9(20), 3494-3505.
[58]
Khandelia, R.; Jaiswal, A.; Ghosh, S.S.; Chattopadhyay, A. Polymer coated gold nanoparticle–protein agglomerates as nanocarriers for hydrophobic drug delivery. J. Mater. Chem. B Mater. Biol. Med., 2014, 2(38), 6472-6477.
[59]
Gu, Z.; Biswas, A.; Zhao, M.; Tang, Y. Tailoring nanocarriers for intracellular protein delivery. Chem. Soc. Rev., 2011, 40(7), 3638-3655.
[60]
Despanie, J.; Dhandhukia, J.P.; Hamm-Alvarez, S.F.; MacKay, J.A. Elastin-like polypeptides: Therapeutic applications for an emerging class of nanomedicines. J. Control. Release, 2016, 240, 93-108.
[61]
Burnett, L.R.; Rahmany, M.B.; Richter, J.R.; Aboushwareb, T.A.; Eberli, D.; Ward, C.L.; Orlando, G.; Hantgan, R.R.; Van Dyke, M.E. Hemostatic properties and the role of cell receptor recognition in human hair keratin protein hydrogels. Biomaterials, 2013, 34(11), 2632-2640.
[62]
Rahmany, M.B.; Hantgan, R.R.; Van Dyke, M. A mechanistic investigation of the effect of keratin-based hemostatic agents on coagulation. Biomaterials, 2013, 34(10), 2492-2500.
[63]
Li, Q.; Zhu, L.; Liu, R.; Huang, D.; Jin, X.; Che, N.; Li, Z.; Qu, X.; Kang, H.; Huang, Y. Biological stimuli responsive drug carriers based on keratin for triggerable drug delivery. J. Mater. Chem., 2012, 22(37), 19964.
[64]
Li, Q.; Yang, S.; Zhu, L.; Kang, H.; Qu, X.; Liu, R.; Huang, Y. Dual-stimuli sensitive keratin graft PHPMA as physiological trigger responsive drug carriers. Polym. Chem., 2015, 6(15), 2869-2878.
[65]
Curcio, M.; Blanco-Fernandez, B.; Diaz-Gomez, L.; Concheiro, A.; Alvarez-Lorenzo, C. Hydrophobically Modified Keratin Vesicles for GSH-Responsive Intracellular Drug Release. Bioconjug. Chem., 2015, 26(9), 1900-1907.
[66]
Zhang, N.; Zhao, F.; Zou, Q.; Li, Y.; Ma, G.; Yan, X. Multitriggered Tumor-Responsive Drug Delivery Vehicles Based on Protein and Polypeptide Coassembly for Enhanced Photodynamic Tumor Ablation. Small, 2016, 12(43), 5936-5943.
[67]
Khandelia, R.; Bhandari, S.; Pan, U.N.; Ghosh, S.S.; Chattopadhyay, A. Gold Nanocluster Embedded Albumin Nanoparticles for Two-Photon Imaging of Cancer Cells Accompanying Drug Delivery. Small, 2015, 11(33), 4075-4081.
[68]
Chen, Q.; Feng, L.; Liu, J.; Zhu, W.; Dong, Z.; Wu, Y.; Liu, Z. Intelligent Albumin-MnO2 Nanoparticles as pH-/H2 O2 -Responsive Dissociable Nanocarriers to Modulate Tumor Hypoxia for Effective Combination Therapy. Adv. Mater., 2016, 28(33), 7129-7136.
[69]
Peppas, N.A.; Khademhosseini, A. Make better, safer biomaterials. Nature, 2016, 540(7633), 335-337.
[70]
Parisi-Amon, A.; Mulyasasmita, W.; Chung, C.; Heilshorn, S.C. Protein-engineered injectable hydrogel to improve retention of transplanted adipose-derived stem cells. Adv. Healthc. Mater., 2013, 2(3), 428-432.
[71]
Davis, N.E.; Beenken-Rothkopf, L.N.; Mirsoian, A.; Kojic, N.; Kaplan, D.L.; Barron, A.E.; Fontaine, M.J. Enhanced function of pancreatic islets co-encapsulated with ECM proteins and mesenchymal stromal cells in a silk hydrogel. Biomaterials, 2012, 33(28), 6691-6697.
[72]
Silva, R.; Fabry, B.; Boccaccini, A.R. Fibrous protein-based hydrogels for cell encapsulation. Biomaterials, 2014, 35(25), 6727-6738.
[73]
Xing, R.; Liu, K.; Jiao, T.; Zhang, N.; Ma, K.; Zhang, R.; Zou, Q.; Ma, G.; Yan, X. An injectable self-assembling collagen-gold hybrid hydrogel for combinatorial antitumor photothermal/photodynamic therapy. Adv. Mater., 2016, 28(19), 3669-3676.
[74]
Annabi, N.; Shin, S.R.; Tamayol, A.; Miscuglio, M.; Bakooshli, M.A.; Assmann, A.; Mostafalu, P.; Sun, J.Y.; Mithieux, S.; Cheung, L.; Tang, X.S.; Weiss, A.S.; Khademhosseini, A. Highly elastic and conductive human-based protein hybrid hydrogels. Adv. Mater., 2016, 28(1), 40-49.
[75]
Su, D.; Jiang, L.; Chen, X.; Dong, J.; Shao, Z. Enhancing the gelation and bioactivity of injectable silk fibroin hydrogel with Laponite nanoplatelets. ACS Appl. Mater. Interfaces, 2016, 8(15), 9619-9628.
[76]
Kim, I.; Choi, J.S.; Lee, S.; Byeon, H.J.; Lee, E.S.; Shin, B.S.; Choi, H.G.; Lee, K.C.; Youn, Y.S. In situ facile-forming PEG cross-linked albumin hydrogels loaded with an apoptotic TRAIL protein. J. Control. Release, 2015, 214, 30-39.
[77]
Asai, D.; Xu, D.; Liu, W.; Garcia Quiroz, F.; Callahan, D.J.; Zalutsky, M.R.; Craig, S.L.; Chilkoti, A. Protein polymer hydrogels by in situ, rapid and reversible self-gelation. Biomaterials, 2012, 33(21), 5451-5458.
[78]
Zhang, Y.N.; Avery, R.K.; Vallmajo-Martin, Q.; Assmann, A.; Vegh, A.; Memic, A.; Olsen, B.D.; Annabi, N.; Khademhosseini, A. A highly elastic and rapidly crosslinkable elastin-like polypeptide-based hydrogel for biomedical applications. Adv. Funct. Mater., 2015, 25(30), 4814-4826.
[79]
Fakhari, A.; Anand Subramony, J. Engineered in-situ depot-forming hydrogels for intratumoral drug delivery. J. Control. Release, 2015, 220(Pt A), 465-475.
[80]
Raja, S.T.; Thiruselvi, T.; Mandal, A.B.; Gnanamani, A. pH and redox sensitive albumin hydrogel: A self-derived biomaterial. Sci. Rep., 2015, 5, 15977.
[81]
Han, S.; Ham, T.R.; Haque, S.; Sparks, J.L.; Saul, J.M. Alkylation of human hair keratin for tunable hydrogel erosion and drug delivery in tissue engineering applications. Acta Biomater., 2015, 23, 201-213.
[82]
Nakata, R.; Osumi, Y.; Miyagawa, S.; Tachibana, A.; Tanabe, T. Preparation of keratin and chemically modified keratin hydrogels and their evaluation as cell substrate with drug releasing ability. J. Biosci. Bioeng., 2015, 120(1), 111-116.
[83]
Lin, J.; Wang, M.; Hu, H.; Yang, X.; Wen, B.; Wang, Z.; Jacobson, O.; Song, J.; Zhang, G.; Niu, G.; Huang, P.; Chen, X. Multimodal-imaging-guided cancer phototherapy by versatile biomimetic theranostics with UV and gamma-irradiation protection. Adv. Mater., 2016, 28(17), 3273-3279.
[84]
Tuin, A.; Kluijtmans, S.G.; Bouwstra, J.B.; Harmsen, M.C.; Van Luyn, M.J. Recombinant gelatin microspheres: novel formulations for tissue repair? Tissue Eng. Part A, 2010, 16(6), 1811-1821.
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