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Bioconjugation in Drug Delivery: Practical Perspectives and Future Perceptions

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Pharmaceutical Nanotechnology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2000))

Abstract

For the past three decades, pharmaceutical research has been mainly converging to novel carrier systems and nanoparticulate colloidal technologies for drug delivery, such as nanoparticles, nanospheres, vesicular systems, liposomes, or nanocapsules to impart novel functions and targeting abilities. Such technologies opened the gate towards more sophisticated and effective multi-acting platform(s) which can offer site-targeting, imaging, and treatment using a single multifunctional system. Unfortunately, such technologies faced major intrinsic hurdles including high cost, low stability profile, short shelf-life, and poor reproducibility across and within production batches leading to harsh bench-to-bedside transformation.

Currently, pharmaceutical industry along with academic research is investing heavily in bioconjugate structures as an appealing and advantageous alternative to nanoparticulate delivery systems with all its flexible benefits when it comes to custom design and tailor grafting along with avoiding most of its shortcomings. Bioconjugation is a ubiquitous technique that finds a multitude of applications in different branches of life sciences, including drug and gene delivery applications, biological assays, imaging, and biosensing.

Bioconjugation is simple, easy, and generally a one-step drug (active pharmaceutical ingredient) conjugation, using various smart biocompatible, bioreducible, or biodegradable linkers, to targeting agents, PEG layer, or another drug. In this chapter, the different types of bioconjugates, the techniques used throughout the course of their synthesis and characterization, as well as the well-established synthetic approaches used for their formulation are presented. In addition, some exemplary representatives are outlined with greater emphasis on the practical tips and tricks of the most prominent techniques such as click chemistry, carbodiimide coupling, and avidin–biotin system.

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References

  1. Hermanson GT (2013) Chapter 1 - introduction to bioconjugation. In: Bioconjugate techniques, 3rd edn. Academic Press, Boston, pp 1–125. https://doi.org/10.1016/B978-0-12-382239-0.00001-7

    Chapter  Google Scholar 

  2. Kalia J, Raines RT (2010) Advances in bioconjugation. Curr Org Chem 14(2):138–147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Vicent MJ, Duncan R (2006) Polymer conjugates: nanosized medicines for treating cancer. Trends Biotechnol 24(1):39–47. https://doi.org/10.1016/j.tibtech.2005.11.006

    Article  CAS  PubMed  Google Scholar 

  4. Duncan R (1992) Drug-polymer conjugates: potential for improved chemotherapy. Anti-Cancer Drugs 3(3):175–210

    Article  CAS  PubMed  Google Scholar 

  5. Duncan R (2006) Polymer conjugates for drug targeting. From inspired to inspiration! J Drug Target 14(6):333–335. https://doi.org/10.1080/10611860600833880

    Article  CAS  PubMed  Google Scholar 

  6. Duncan R (2006) Polymer conjugates as anticancer nanomedicines. Nat Rev Cancer 6(9):688–701. https://doi.org/10.1038/nrc1958

    Article  CAS  PubMed  Google Scholar 

  7. Faghihnejad A, Feldman KE, Yu J, Tirrell MV, Israelachvili JN, Hawker CJ, Kramer EJ, Zeng H (2014) Adhesion and surface interactions of a self-healing polymer with multiple hydrogen-bonding groups. Adv Funct Mater 24(16):2322–2333. https://doi.org/10.1002/adfm.201303013

    Article  CAS  Google Scholar 

  8. Geyik C, Evran S, Timur S, Telefoncu A (2014) The covalent bioconjugate of multiwalled carbon nanotube and amino-modified linearized plasmid DNA for gene delivery. Biotechnol Prog 30(1):224–232. https://doi.org/10.1002/btpr.1836

    Article  CAS  PubMed  Google Scholar 

  9. Duncan R (2003) The dawning era of polymer therapeutics. Nat Rev Drug Discov 2(5):347–360. https://doi.org/10.1038/nrd1088

    Article  CAS  PubMed  Google Scholar 

  10. Kroon J, Metselaar JM, Storm G, van der Pluijm G (2014) Liposomal nanomedicines in the treatment of prostate cancer. Cancer Treat Rev 40(4):578–584. https://doi.org/10.1016/j.ctrv.2013.10.005

    Article  CAS  PubMed  Google Scholar 

  11. Niraula S, Seruga B, Ocana A, Shao T, Goldstein R, Tannock IF, Amir E (2012) The price we pay for progress: a meta-analysis of harms of newly approved anticancer drugs. J Clin Oncol 30(24):3012–3019. https://doi.org/10.1200/JCO.2011.40.3824

    Article  PubMed  Google Scholar 

  12. Solyanik GI (2010) Multifactorial nature of tumor drug resistance. Exp Oncol 32(3):181–185

    CAS  PubMed  Google Scholar 

  13. Chari RVJ, Miller ML, Widdison WC (2014) Antibody–drug conjugates: an emerging concept in Cancer therapy. Angew Chem Int Ed 53(15):3796–3827. https://doi.org/10.1002/anie.201307628

    Article  CAS  Google Scholar 

  14. Kim EG, Kim KM (2015) Strategies and advancement in antibody-drug conjugate optimization for targeted Cancer therapeutics. Biomol Ther (Seoul) 23(6):493–509. https://doi.org/10.4062/biomolther.2015.116

    Article  CAS  Google Scholar 

  15. Diamantis N, Banerji U (2016) Antibody-drug conjugates—an emerging class of cancer treatment. Br J Cancer 114(4):362–367. https://doi.org/10.1038/bjc.2015.435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ravin HA, Seligman AM, Fine J (1952) Polyvinyl pyrrolidone as a plasma expander; studies on its excretion, distribution and metabolism. N Engl J Med 247(24):921–929. https://doi.org/10.1056/nejm195212112472403

    Article  CAS  PubMed  Google Scholar 

  17. Shelanski HA, Shelanski MV (1956) PVP-iodine: history, toxicity and therapeutic uses. J Int Coll Surg 25(6):727–734

    CAS  PubMed  Google Scholar 

  18. Ringsdorf H (1975) Structure and properties of pharmacologically active polymers. J Polym Sci: Polym Symp 51(1):135–153. https://doi.org/10.1002/polc.5070510111

    Article  CAS  Google Scholar 

  19. Matsumura Y, Maeda H (1986) A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res 46(12 Pt 1):6387–6392

    CAS  PubMed  Google Scholar 

  20. Meerum Terwogt JM, ten Bokkel Huinink WW, Schellens JH, Schot M, Mandjes IA, Zurlo MG, Rocchetti M, Rosing H, Koopman FJ, Beijnen JH (2001) Phase I clinical and pharmacokinetic study of PNU166945, a novel water-soluble polymer-conjugated prodrug of paclitaxel. Anti-Cancer Drugs 12(4):315–323

    Article  CAS  PubMed  Google Scholar 

  21. Wachters FM, Groen HJM, Maring JG, Gietema JA, Porro M, Dumez H, de Vries EGE, van Oosterom AT (2004) A phase I study with MAG-camptothecin intravenously administered weekly for 3 weeks in a 4-week cycle in adult patients with solid tumours. Br J Cancer 90(12):2261–2267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Duncan R, Vicent MJ (2010) Do HPMA copolymer conjugates have a future as clinically useful nanomedicines? A critical overview of current status and future opportunities. Adv Drug Deliv Rev 62(2):272–282. https://doi.org/10.1016/j.addr.2009.12.005

    Article  CAS  PubMed  Google Scholar 

  23. Larson N, Ghandehari H (2012) Polymeric conjugates for drug delivery. Chem Mater 24(5):840–853. https://doi.org/10.1021/cm2031569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Veronese FM, Harris JM (2002) Introduction and overview of peptide and protein pegylation. Adv Drug Deliv Rev 54(4):453–456

    Article  CAS  PubMed  Google Scholar 

  25. Pasut G, Sergi M, Veronese FM (2008) Anti-cancer PEG-enzymes: 30 years old, but still a current approach. Adv Drug Deliv Rev 60(1):69–78. https://doi.org/10.1016/j.addr.2007.04.018

    Article  CAS  PubMed  Google Scholar 

  26. Bailon P, Palleroni A, Schaffer CA, Spence CL, Fung W-J, Porter JE, Ehrlich GK, Pan W, Xu Z-X, Modi MW, Farid A, Berthold W, Graves M (2001) Rational design of a potent, long-lasting form of interferon: a 40 kDa branched polyethylene glycol-conjugated interferon α-2a for the treatment of hepatitis C. Bioconjug Chem 12(2):195–202. https://doi.org/10.1021/bc000082g

    Article  CAS  PubMed  Google Scholar 

  27. Wang YS, Youngster S, Grace M, Bausch J, Bordens R, Wyss DF (2002) Structural and biological characterization of pegylated recombinant interferon alpha-2b and its therapeutic implications. Adv Drug Deliv Rev 54(4):547–570

    Article  CAS  PubMed  Google Scholar 

  28. Roelfsema F, Biermasz NR, Pereira AM, Romijn JM (2006) Nanomedicines in the treatment of acromegaly: focus on pegvisomant. Int J Nanomedicine 1(4):385–398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Trainer PJ, Drake WM, Katznelson L, Freda PU, Herman-Bonert V, van der Lely AJ, Dimaraki EV, Stewart PM, Friend KE, Vance ML, Besser GM, Scarlett JA, Thorner MO, Parkinson C, Klibanski A, Powell JS, Barkan AL, Sheppard MC, Malsonado M, Rose DR, Clemmons DR, Johannsson G, Bengtsson BA, Stavrou S, Kleinberg DL, Cook DM, Phillips LS, Bidlingmaier M, Strasburger CJ, Hackett S, Zib K, Bennett WF, Davis RJ (2000) Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 342(16):1171–1177. https://doi.org/10.1056/nejm200004203421604

    Article  CAS  PubMed  Google Scholar 

  30. Rowinsky EK, Rizzo J, Ochoa L, Takimoto CH, Forouzesh B, Schwartz G, Hammond LA, Patnaik A, Kwiatek J, Goetz A, Denis L, McGuire J, Tolcher AW (2003) A phase I and pharmacokinetic study of pegylated camptothecin as a 1-hour infusion every 3 weeks in patients with advanced solid malignancies. J Clin Oncol 21(1):148–157. https://doi.org/10.1200/jco.2003.03.143

    Article  CAS  PubMed  Google Scholar 

  31. Fang J, Nakamura H, Maeda H (2011) The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev 63(3):136–151. https://doi.org/10.1016/j.addr.2010.04.009

    Article  CAS  PubMed  Google Scholar 

  32. Duncan R (2009) Development of HPMA copolymer–anticancer conjugates: clinical experience and lessons learnt. Adv Drug Deliv Rev 61(13):1131–1148. https://doi.org/10.1016/j.addr.2009.05.007

    Article  CAS  PubMed  Google Scholar 

  33. Kopecek J, Kopeckova P (2010) HPMA copolymers: origins, early developments, present, and future. Adv Drug Deliv Rev 62(2):122–149. https://doi.org/10.1016/j.addr.2009.10.004

    Article  CAS  PubMed  Google Scholar 

  34. Lammers T (2010) Improving the efficacy of combined modality anticancer therapy using HPMA copolymer-based nanomedicine formulations. Advanced Drug Deliv Rev 62(2):203–230. https://doi.org/10.1016/j.addr.2009.11.028

    Article  CAS  Google Scholar 

  35. Caiolfa VR, Zamai M, Fiorino A, Frigerio E, Pellizzoni C, d’Argy R, Ghiglieri A, Castelli MG, Farao M, Pesenti E, Gigli M, Angelucci F, Suarato A (2000) Polymer-bound camptothecin: initial biodistribution and antitumour activity studies. J Control Release 65(1–2):105–119. https://doi.org/10.1016/S0168-3659(99)00243-6

    Article  CAS  PubMed  Google Scholar 

  36. Rademaker-Lakhai JM, Terret C, Howell SB, Baud CM, de Boer RF, Pluim D, Beijnen JH, Schellens JHM, Droz J-P (2004) A phase I and pharmacological study of the platinum polymer AP5280 given as an intravenous infusion once every 3 weeks in patients with solid tumors. Clin Cancer Res 10(10):3386–3395. https://doi.org/10.1158/1078-0432.ccr-03-0315

    Article  CAS  PubMed  Google Scholar 

  37. L-d Q, Yuan F, X-m L, J-g H, Alnouti Y, Wang D (2010) Pharmacokinetic and biodistribution studies of N-(2-Hydroxypropyl)methacrylamide copolymer-dexamethasone conjugates in adjuvant-induced arthritis rat model. Mol Pharm 7(4):1041–1049. https://doi.org/10.1021/mp100132h

    Article  CAS  Google Scholar 

  38. Lammers T, Subr V, Ulbrich K, Peschke P, Huber PE, Hennink WE, Storm G (2009) Simultaneous delivery of doxorubicin and gemcitabine to tumors in vivo using prototypic polymeric drug carriers. Biomaterials 30(20):3466–3475. https://doi.org/10.1016/j.biomaterials.2009.02.040

    Article  CAS  PubMed  Google Scholar 

  39. Kasuya Y, Lu ZR, Kopeckova P, Minko T, Tabibi SE, Kopecek J (2001) Synthesis and characterization of HPMA copolymer-aminopropylgeldanamycin conjugates. J Control Release 74(1–3):203–211

    Article  CAS  PubMed  Google Scholar 

  40. Tomalia D, Baker H, Dewald J, Hall M, Kallos G, Martin S, Roeck J, Ryder J, Smith P (1985) A new class of polymers: starburst-dendritic. Polym J 17(1):117–132

    Article  CAS  Google Scholar 

  41. Tomalia DA, Baker H, Dewald J, Hall M, Kallos G, Martin S, Roeck J, Ryder J, Smith P (1986) Dendritic macromolecules: synthesis of starburst dendrimers. Macromolecules 19(9):2466–2468

    Article  CAS  Google Scholar 

  42. Thiagarajan G, Ray A, Malugin A, Ghandehari H (2010) PAMAM-Camptothecin conjugate inhibits proliferation and induces nuclear fragmentation in colorectal carcinoma cells. Pharm Res 27(11):2307–2316. https://doi.org/10.1007/s11095-010-0179-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Menjoge AR, Kannan RM, Tomalia DA (2010) Dendrimer-based drug and imaging conjugates: design considerations for nanomedical applications. Drug Discov Today 15(5–6):171–185. https://doi.org/10.1016/j.drudis.2010.01.009

    Article  CAS  PubMed  Google Scholar 

  44. Majoros IJ, Williams CR, Becker A, Baker JR (2009) Methotrexate delivery via folate targeted dendrimer-based nanotherapeutic platform. Wiley Interdiscip Rev Nanomed Nanobiotechnol 1(5):502–510. https://doi.org/10.1002/wnan.37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Cheng Y, Zhao L, Li Y, Xu T (2011) Design of biocompatible dendrimers for cancer diagnosis and therapy: current status and future perspectives. Chem Soc Rev 40(5):2673–2703. https://doi.org/10.1039/c0cs00097c

    Article  CAS  PubMed  Google Scholar 

  46. Sun H, Meng F, Dias AA, Hendriks M, Feijen J, Zhong Z (2011) α-Amino acid containing degradable polymers as functional biomaterials: rational design, synthetic pathway, and biomedical applications. Biomacromolecules 12(6):1937–1955. https://doi.org/10.1021/bm200043u

    Article  CAS  PubMed  Google Scholar 

  47. Couffin-Hoarau AC, Aubertin AM, Boustta M, Schmidt S, Fehrentz JA, Martinez J, Vert M (2009) Peptide-poly(L-lysine citramide) conjugates and their in vitro anti-HIV behavior. Biomacromolecules 10(4):865–876. https://doi.org/10.1021/bm801376v

    Article  CAS  PubMed  Google Scholar 

  48. Yang D, Van S, Liu J, Wang J, Jiang X, Wang Y, Yu L (2011) Physicochemical properties and biocompatibility of a polymer-paclitaxel conjugate for cancer treatment. Int J Nanomedicine 6:2557–2566. https://doi.org/10.2147/ijn.s25044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Metselaar JM, Bruin P, de Boer LW, de Vringer T, Snel C, Oussoren C, Wauben MH, Crommelin DJ, Storm G, Hennink WE (2003) A novel family of L-amino acid-based biodegradable polymer-lipid conjugates for the development of long-circulating liposomes with effective drug-targeting capacity. Bioconjug Chem 14(6):1156–1164. https://doi.org/10.1021/bc0340363

    Article  CAS  PubMed  Google Scholar 

  50. Baldwin AD, Kiick KL (2010) Polysaccharide-modified synthetic polymeric biomaterials. Biopolymers 94(1):128–140. https://doi.org/10.1002/bip.21334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kemp JD, Cardillo T, Stewart BC, Kehrberg E, Weiner G, Hedlund B, Naumann PW (1995) Inhibition of lymphoma growth <em>in vivo</em> by combined treatment with Hydroxyethyl starch Deferoxamine conjugate and IgG monoclonal antibodies against the transferrin receptor. Cancer Res 55(17):3817–3824

    CAS  PubMed  Google Scholar 

  52. Pisal DS, Kosloski MP, Balu-Iyer SV (2010) Delivery of therapeutic proteins. J Pharm Sci 99(6):2557–2575. https://doi.org/10.1002/jps.22054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Yurkovetskiy AV, Fram RJ (2009) XMT-1001, a novel polymeric camptothecin pro-drug in clinical development for patients with advanced cancer. Adv Drug Deliv Rev 61(13):1193–1202. https://doi.org/10.1016/j.addr.2009.01.007

    Article  CAS  PubMed  Google Scholar 

  54. Torchilin V (2009) Multifunctional and stimuli-sensitive pharmaceutical nanocarriers. Eur J Pharm Biopharm 71(3):431–444. https://doi.org/10.1016/j.ejpb.2008.09.026

    Article  CAS  PubMed  Google Scholar 

  55. Vaupel P, Kallinowski F, Okunieff P (1989) Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res 49(23):6449–6465

    CAS  PubMed  Google Scholar 

  56. Bawa P, Pillay V, Choonara YE, du Toit LC (2009) Stimuli-responsive polymers and their applications in drug delivery. Biomed Mater 4(2):022001. https://doi.org/10.1088/1748-6041/4/2/022001

    Article  CAS  PubMed  Google Scholar 

  57. Ulbrich K, Etrych T, Chytil P, Jelınková M, Řıhová B (2003) HPMA copolymers with pH-controlled release of doxorubicin: in vitro cytotoxicity and in vivo antitumor activity. J Control Release 87(1–3):33–47. https://doi.org/10.1016/S0168-3659(02)00348-6

    Article  CAS  PubMed  Google Scholar 

  58. Chilkoti A, Dreher MR, Meyer DE, Raucher D (2002) Targeted drug delivery by thermally responsive polymers. Adv Drug Deliv Rev 54(5):613–630. https://doi.org/10.1016/S0169-409X(02)00041-8

    Article  CAS  PubMed  Google Scholar 

  59. de Castro MDL, Capote FP, Ávila NS (2008) Is dialysis alive as a membrane-based separation technique? TrAC Trend Anal Chem 27(4):315–326. https://doi.org/10.1016/j.trac.2008.01.015

    Article  CAS  Google Scholar 

  60. Luo J, Wu C, Xu T, Wu Y (2011) Diffusion dialysis-concept, principle and applications. J Membr Sci 366(1–2):1–16. https://doi.org/10.1016/j.memsci.2010.10.028

    Article  CAS  Google Scholar 

  61. Silva MM, Krug FJ, Oliveira PV, Nóbrega JA, Reis BF, Penteado DAG (1996) Separation and preconcentration by flow injection coupled to tungsten coil electrothermal atomic absorption spectrometry. Spectrochim Acta Part B: At Spectrosc 51(14):1925–1934. https://doi.org/10.1016/S0584-8547(96)01536-4

    Article  Google Scholar 

  62. Sajid M, Kawde A-N, Daud M (2015) Designs, formats and applications of lateral flow assay: a literature review. J Saudi Chem Soc 19(6):689–705. https://doi.org/10.1016/j.jscs.2014.09.001

    Article  Google Scholar 

  63. Yeh HM, Chen HY, Chen KT (2000) Membrane ultrafiltration in a tubular module with a steel rod inserted concentrically for improved performance. J Membr Sci 168(1–2):121–133. https://doi.org/10.1016/S0376-7388(99)00315-4

    Article  CAS  Google Scholar 

  64. Beckmann W (2013) Crystallization: introduction. In: Crystallization. Wiley-VCH Verlag GmbH & Co, KGaA, pp 1–5. https://doi.org/10.1002/9783527650323.ch1

    Chapter  Google Scholar 

  65. Mersmann A (1995) Crystallization technology handbook. Dry Technol 13(4):1037–1038. https://doi.org/10.1080/07373939508917003

    Article  Google Scholar 

  66. Dhanaraj G, Byrappa K, Prasad V, Dudley M (2010) Crystal growth techniques and characterization: an overview. In: Dhanaraj G, Byrappa K, Prasad V, Dudley M (eds) Springer handbook of crystal growth. Springer, Berlin Heidelberg, Berlin, Heidelberg, pp 3–16. https://doi.org/10.1007/978-3-540-74761-1_1

    Chapter  Google Scholar 

  67. Beckmann W (2013) Basics of industrial crystallization from solution. In: Crystallization. Wiley-VCH Verlag GmbH & Co, KGaA, pp 173–185. https://doi.org/10.1002/9783527650323.ch9

    Chapter  Google Scholar 

  68. Pirrung MC (2017) 12 - Evaporation. In: Handbook of synthetic organic chemistry, 2nd edn. Academic Press, pp 139–142. https://doi.org/10.1016/B978-0-12-809504-1.00012-1

    Chapter  Google Scholar 

  69. Adams G (2007) The principles of freeze-drying. Methods Mol Biol 368:15–38. https://doi.org/10.1007/978-1-59745-362-2_2

    Article  CAS  PubMed  Google Scholar 

  70. Perry SG, Amos R, Brewer PI (1972) The technique of thin-layer chromatography. In: Practical liquid chromatography. Springer US, Boston, MA, pp 115–164. https://doi.org/10.1007/978-1-4684-1935-1_6

    Chapter  Google Scholar 

  71. Smith I, Ersser RS (1976) Introduction to paper and thin layer chromatography. In: Seakins ISWT (ed) Paper and thin layer chromatography, 4th edn. Butterworth-Heinemann, pp 5–11. https://doi.org/10.1016/B978-0-8151-7839-2.50007-6

    Chapter  Google Scholar 

  72. Kaddi CD, Bennett RV, Paine MRL, Banks MD, Weber AL, Fernández FM, Wang MD (2016) DetectTLC: automated reaction mixture screening utilizing quantitative mass spectrometry image feature. J Am Soc Mass Spectrom 27(2):359–365. https://doi.org/10.1007/s13361-015-1293-9

    Article  CAS  PubMed  Google Scholar 

  73. Santiago M, Strobel S (2013) Thin layer chromatography. Methods Enzymol 533:303–324. https://doi.org/10.1016/b978-0-12-420067-8.00024-6

    Article  CAS  PubMed  Google Scholar 

  74. Wall PE (2006) Sample application. In: Thin-layer chromatography: a modern practical approach. The Royal Society of Chemistry, pp 65–85. https://doi.org/10.1039/9781847552464-00065

  75. Ahadi A, Partoazar A, Abedi-Khorasgani M-H, Shetab-Boushehri SV (2011) Comparison of liquid-liquid extraction-thin layer chromatography with solid-phase extraction-high-performance thin layer chromatography in detection of urinary morphine. J Biomed Res 25(5):362–367. https://doi.org/10.1016/S1674-8301(11)60048-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Wiemer B (1988) F. Geiss: fundamentals of thin layer chromatography planar chromatography. Dr. A. Hüthig Verlag., 1987, 482 S., 202 Abb., 40 tab., DM 192,–, ISBN 3-7785-0854-7. Acta Hydrochim Hydrobiol 16(6):653–653, Heidelberg. https://doi.org/10.1002/aheh.19880160622

    Article  Google Scholar 

  77. Ettre LS, Sakodynskii KI (1993) M. S. Tswett and the discovery of chromatography I: Early work (1899–1903). Chromatographia 35(3–4):223–231. https://doi.org/10.1007/BF02269707

    Article  CAS  Google Scholar 

  78. Scott RPW (2012) Liquid chromatography (Chrom-Ed series). Reese-Scott Partnership, 1st edn, 23 Jan 2012

    Google Scholar 

  79. Martin AJP, Synge RLM (1941) A new form of chromatogram employing two liquid phases: a theory of chromatography. 2. Application to the micro-determination of the higher monoamino-acids in proteins. Biochem J 35(12):1358–1368

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Lathe GH, Ruthven CRJ (1956) The separation of substances and estimation of their relative molecular sizes by the use of columns of starch in water. Biochem J 62(4):665–674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Porath J, Flodin P (1959) Gel filtration: a method for desalting and group separation. Nature 183(4676):1657–1659

    Article  CAS  PubMed  Google Scholar 

  82. Hjerten S, Mosbach R (1962) "Molecular-sieve" chromatography of proteins on columns of cross-linked polyacrylamide. Anal Biochem 3:109–118

    Article  CAS  PubMed  Google Scholar 

  83. Polson A (1961) Fractionation of protein mixtures on columns of granulated agar. Biochim Biophys Acta 50:565–567

    Article  CAS  PubMed  Google Scholar 

  84. Paul-Dauphin S, Karaca F, Morgan TJ, Millan-Agorio M, Herod AA, Kandiyoti R (2007) Probing size exclusion mechanisms of complex hydrocarbon mixtures: the effect of altering eluent compositions. Energy Fuel 21(6):3484–3489. https://doi.org/10.1021/ef700410e

    Article  CAS  Google Scholar 

  85. Berek D (2010) Size exclusion chromatography – a blessing and a curse of science and technology of synthetic polymers. J Sep Sci 33(3):315–335. https://doi.org/10.1002/jssc.200900709

    Article  CAS  PubMed  Google Scholar 

  86. Wang J, Huang X, Ruan L, Lan T, Ren J (2013) Size exclusion chromatography as a universal method for the purification of quantum dots bioconjugates. Electrophoresis 34(12):1764–1771. https://doi.org/10.1002/elps.201200649

    Article  CAS  PubMed  Google Scholar 

  87. Douville V, Lodi A, Miller J, Nicolas A, Clarot I, Prilleux B, Megoulas N, Koupparis M (2006) Evaporative light scattering detection (ELSD): a tool for improved quality control of drug substances. Pharmeur Sci Notes 2006(1):9–15

    CAS  PubMed  Google Scholar 

  88. Viegas A, Macedo AL, Cabrita EJ (2009) Ligand-based nuclear magnetic resonance screening techniques. Methods Mol Biol 572:81–100. https://doi.org/10.1007/978-1-60761-244-5_6

    Article  CAS  PubMed  Google Scholar 

  89. Balci M (2005) 1 - Introduction. In: Basic 1H- and 13C-NMR spectroscopy. Elsevier Science, Amsterdam, pp 3–8. https://doi.org/10.1016/B978-044451811-8.50001-2

    Chapter  Google Scholar 

  90. Bharti SK, Roy R (2012) Quantitative 1H NMR spectroscopy. TrAC Trend Anal Chem 35:5–26. https://doi.org/10.1016/j.trac.2012.02.007

    Article  CAS  Google Scholar 

  91. Jacobsen NE (2007) Interpretation of proton (1H) NMR spectra. In: NMR spectroscopy explained. John Wiley & Sons, pp 39–73. https://doi.org/10.1002/9780470173350.ch2

  92. Jungnickel JL, Forbes JW (1963) Quantitative measurement of hydrogen types by Intergrated nuclear magnetic resonance intensities. Anal Chem 35(8):938–942. https://doi.org/10.1021/ac60201a005

    Article  CAS  Google Scholar 

  93. Balci M (2005) 8 - dynamic NMR spectroscopy. In: Basic 1H- and 13C-NMR spectroscopy. Elsevier Science, Amsterdam, pp 213–231. https://doi.org/10.1016/B978-044451811-8.50008-5

    Chapter  Google Scholar 

  94. Creary X, Anderson A, Brophy C, Crowell F, Funk Z (2012) Method for assigning structure of 1,2,3-triazoles. J Org Chem 77(19):8756–8761. https://doi.org/10.1021/jo301265t

    Article  CAS  PubMed  Google Scholar 

  95. Nishizawa K, Takai M, Ishihara K (2011) A bioconjugated phospholipid polymer biointerface with nanometer-scaled structure for highly sensitive immunoassays. Methods Mol Biol 751:491–502. https://doi.org/10.1007/978-1-61779-151-2_31

    Article  CAS  PubMed  Google Scholar 

  96. Balci M (2005) 13 - 13C chemical shifts of organic compounds. In: Basic 1H- and 13C-NMR spectroscopy. Elsevier Science, Amsterdam, pp 293–324. https://doi.org/10.1016/B978-044451811-8.50013-9

    Chapter  Google Scholar 

  97. Sakata K, Uzawa J, Sakurai A (1977) Application of carbon-13 n.m.r. Spectroscopy to the structural investigation of ezomycins. Org Magn Reson 10(1):230–234. https://doi.org/10.1002/mrc.1270100152

    Article  CAS  Google Scholar 

  98. Jacobsen NE (2007) Carbon-13 (13C) NMR spectroscopy. In: NMR spectroscopy explained. John Wiley & Sons, pp 135–154. https://doi.org/10.1002/9780470173350.ch4

  99. Breitmaier E (2002) Short introduction to basic principles and methods. In: Structure elucidation by NMR in organic chemistry. John Wiley & Sons, pp 1–10. https://doi.org/10.1002/0470853069.ch1

  100. Mancini L, Payne GS, Leach MO (2003) Comparison of polarization transfer sequences for enhancement of signals in clinical 31P MRS studies. Magn Reson Med 50(3):578–588. https://doi.org/10.1002/mrm.10551

    Article  PubMed  Google Scholar 

  101. Singhal N, Kumar M, Kanaujia PK, Virdi JS (2015) MALDI-TOF mass spectrometry: an emerging technology for microbial identification and diagnosis. Front Microbiol 6:791. https://doi.org/10.3389/fmicb.2015.00791

    Article  PubMed  PubMed Central  Google Scholar 

  102. Lavigne JP, Espinal P, Dunyach-Remy C, Messad N, Pantel A, Sotto A (2013) Mass spectrometry: a revolution in clinical microbiology? Clin Chem Lab Med 51(2):257–270. https://doi.org/10.1515/cclm-2012-0291

    Article  CAS  PubMed  Google Scholar 

  103. Susnea I, Bernevic B, Wicke M, Ma L, Liu S, Schellander K, Przybylski M (2013) Application of MALDI-TOF-mass spectrometry to proteome analysis using stain-free gel electrophoresis. Top Curr Chem 331:37–54. https://doi.org/10.1007/128_2012_321

    Article  CAS  PubMed  Google Scholar 

  104. Calderaro A, Arcangeletti M-C, Rodighiero I, Buttrini M, Gorrini C, Motta F, Germini D, Medici M-C, Chezzi C, De Conto F (2014) Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry applied to virus identification. Sci Rep 4:6803. https://doi.org/10.1038/srep06803. http://www.nature.com/articles/srep06803 - supplementary-information

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Wang H, Zhao Z, Guo Y (2013) Chemical and Biochemical applications of MALDI TOF-MS based on analyzing the small organic compounds. In: Cai Z, Liu S (eds) Applications of MALDI-TOF spectroscopy. Springer, Berlin Heidelberg, pp 165–192. https://doi.org/10.1007/128_2012_364

    Chapter  Google Scholar 

  106. Machado YJ, Rabasa Y, Montesinos R, Cremata J, Besada V, Fuentes D, Castillo A, de la Luz KR, Vázquez AM, Himly M (2011) Physicochemical and biological characterization of 1E10 anti-Idiotype vaccine. BMC Biotechnol 11:112–112. https://doi.org/10.1186/1472-6750-11-112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Stuart BH (2005) Introduction. In: Infrared spectroscopy: fundamentals and applications. John Wiley & Sons, pp 1–13. https://doi.org/10.1002/0470011149.ch1

  108. Blinder SM (2004) Introduction to quantum mechanics: in chemistry, materials science, and biology. Elsevier

    Google Scholar 

  109. Ojeda JJ, Dittrich M (2012) Fourier transform infrared spectroscopy for molecular analysis of microbial cells. Methods Mol Biol 881:187–211. https://doi.org/10.1007/978-1-61779-827-6_8

    Article  CAS  PubMed  Google Scholar 

  110. Skoog DA, Crouch SR, Holler FJ (2007) Principles of instrumental analysis. Thomson Brooks/Cole, Belmont, CA

    Google Scholar 

  111. Abbas O, Dardenne P, Baeten V (2012) Chapter 3 - near-infrared, mid-infrared, and Raman spectroscopy. In: Picó Y (ed) Chemical analysis of food: techniques and applications. Academic Press, Boston, pp 59–89. https://doi.org/10.1016/B978-0-12-384862-8.00003-0

    Chapter  Google Scholar 

  112. Tanaka K, Kanazawa T, Horiuchi S, Ando T, Sugawara K, Takashima Y, Seta Y, Okada H (2013) Cytoplasm-responsive nanocarriers conjugated with a functional cell-penetrating peptide for systemic siRNA delivery. Int J Pharm 455(1–2):40–47. https://doi.org/10.1016/j.ijpharm.2013.07.069

    Article  CAS  PubMed  Google Scholar 

  113. Taranejoo S, Chandrasekaran R, Cheng W, Hourigan K (2016) Bioreducible PEI-functionalized glycol chitosan: a novel gene vector with reduced cytotoxicity and improved transfection efficiency. Carbohydr Polym 153:160–168. https://doi.org/10.1016/j.carbpol.2016.07.080

    Article  CAS  PubMed  Google Scholar 

  114. Knapinska AM, Tokmina-Roszyk D, Amar S, Tokmina-Roszyk M, Mochalin VN, Gogotsi Y, Cosme P, Terentis AC, Fields GB (2015) Solid-phase synthesis, characterization, and cellular activities of collagen-model nanodiamond-peptide conjugates. Biopolymers 104(3):186–195. https://doi.org/10.1002/bip.22636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Imani R, Emami SH, Faghihi S (2015) Synthesis and characterization of an octaarginine functionalized graphene oxide nano-carrier for gene delivery applications. Phys Chem Chem Phys 17(9):6328–6339. https://doi.org/10.1039/c4cp04301d

    Article  CAS  PubMed  Google Scholar 

  116. Kolb HC, Finn MG, Sharpless KB (2001) Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed Engl 40(11):2004–2021

    Article  CAS  PubMed  Google Scholar 

  117. Tornoe CW, Christensen C, Meldal M (2002) Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(i)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J Org Chem 67(9):3057–3064

    Article  CAS  PubMed  Google Scholar 

  118. Wang X, Huang B, Liu X, Zhan P (2016) Discovery of bioactive molecules from CuAAC click-chemistry-based combinatorial libraries. Drug Discov Today 21(1):118–132. https://doi.org/10.1016/j.drudis.2015.08.004

    Article  CAS  PubMed  Google Scholar 

  119. Hermanson GT (2013) Chapter 17 - Chemoselective ligation; bioorthogonal reagents. In: Bioconjugate techniques, 3rd edn. Academic Press, Boston, pp 757–785. https://doi.org/10.1016/B978-0-12-382239-0.00017-0

    Chapter  Google Scholar 

  120. Wang C, Ikhlef D, Kahlal S, Saillard J-Y, Astruc D (2016) Metal-catalyzed azide-alkyne “click” reactions: mechanistic overview and recent trends. Coordin Chem Rev 316:1–20. https://doi.org/10.1016/j.ccr.2016.02.010

    Article  CAS  Google Scholar 

  121. Worrell BT, Malik JA, Fokin VV (2013) Direct evidence of a dinuclear copper intermediate in Cu(I)-catalyzed azide-alkyne cycloadditions. Science (New York, NY) 340(6131):457–460. https://doi.org/10.1126/science.1229506

    Article  CAS  Google Scholar 

  122. Massarotti A, Aprile S, Mercalli V, Del Grosso E, Grosa G, Sorba G, Tron GC (2014) Are 1,4- and 1,5-disubstituted 1,2,3-triazoles good pharmacophoric groups? ChemMedChem 9(11):2497–2508. https://doi.org/10.1002/cmdc.201402233

    Article  CAS  PubMed  Google Scholar 

  123. Kolb HC, Sharpless KB (2003) The growing impact of click chemistry on drug discovery. Drug Discov Today 8(24):1128–1137. https://doi.org/10.1016/S1359-6446(03)02933-7

    Article  CAS  PubMed  Google Scholar 

  124. Jewett JC, Bertozzi CR (2010) Cu-free click cycloaddition reactions in chemical biology. Chem Soc Rev 39(4):1272–1279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Prescher JA, Bertozzi CR (2005) Chemistry in living systems. Nat Chem Biol 1(1):13–21. https://doi.org/10.1038/nchembio0605-13

    Article  CAS  PubMed  Google Scholar 

  126. Jarrad AM, Karoli T, Debnath A, Tay CY, Huang JX, Kaeslin G, Elliott AG, Miyamoto Y, Ramu S, Kavanagh AM, Zuegg J, Eckmann L, Blaskovich MAT, Cooper MA (2015) Metronidazole-triazole conjugates: activity against Clostridium difficile and parasites. Eur J Med Chem 101:96–102. https://doi.org/10.1016/j.ejmech.2015.06.019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Negi B, Kumar D, Kumbukgolla W, Jayaweera S, Ponnan P, Singh R, Agarwal S, Rawat DS (2016) Anti-methicillin resistant Staphylococcus aureus activity, synergism with oxacillin and molecular docking studies of metronidazole-triazole hybrids. Eur J Med Chem 115:426–437. https://doi.org/10.1016/j.ejmech.2016.03.041

    Article  CAS  PubMed  Google Scholar 

  128. Link AJ, Vink MK, Tirrell DA (2004) Presentation and detection of azide functionality in bacterial cell surface proteins. J Am Chem Soc 126(34):10598–10602. https://doi.org/10.1021/ja047629c

    Article  CAS  PubMed  Google Scholar 

  129. Lo Conte M, Pacifico S, Chambery A, Marra A, Dondoni A (2010) Photoinduced addition of glycosyl thiols to alkynyl peptides: use of free-radical thiol-yne coupling for post-translational double-glycosylation of peptides. J Org Chem 75(13):4644–4647. https://doi.org/10.1021/jo1008178

    Article  CAS  PubMed  Google Scholar 

  130. Clayton R, Ramsden CA (2005) N-vinyl-Nitroimidazole Cycloadditions: potential routes to nucleoside analogues. Synthesis 2005(16):2695–2700. https://doi.org/10.1055/s-2005-872083

    Article  CAS  Google Scholar 

  131. Zhang W, Li Z, Zhou M, Wu F, Hou X, Luo H, Liu H, Han X, Yan G, Ding Z, Li R (2014) Synthesis and biological evaluation of 4-(1,2,3-triazol-1-yl)coumarin derivatives as potential antitumor agents. Bioorg Med Chem Lett 24(3):799–807. https://doi.org/10.1016/j.bmcl.2013.12.095

    Article  CAS  PubMed  Google Scholar 

  132. Hermanson GT (2013) Chapter 4 - zero-length crosslinkers. In: Bioconjugate techniques, 3rd edn. Academic Press, Boston, pp 259–273. https://doi.org/10.1016/B978-0-12-382239-0.00004-2

    Chapter  Google Scholar 

  133. Williams A, Ibrahim IT (1981) A new mechanism involving cyclic tautomers for the reaction with nucleophiles of the water-soluble peptide coupling reagent 1-ethyl-3-(3′-(dimethylamino)propyl)carbodiimide (EDC). J Am Chem Soc 103(24):7090–7095. https://doi.org/10.1021/ja00414a011

    Article  CAS  Google Scholar 

  134. Sheehan J, Cruickshank P, Boshart G (1961) Notes- a convenient synthesis of water-soluble carbodiimides. J Org Chem 26(7):2525–2528. https://doi.org/10.1021/jo01351a600

    Article  CAS  Google Scholar 

  135. Nakajima N, Ikada Y (1995) Mechanism of amide formation by carbodiimide for bioconjugation in aqueous media. Bioconjug Chem 6(1):123–130. https://doi.org/10.1021/bc00031a015

    Article  CAS  PubMed  Google Scholar 

  136. Young J-J, Cheng K-M, Tsou T-L, Liu H-W, Wang H-J (2004) Preparation of cross-linked hyaluronic acid film using 2-chloro-1-methylpyridinium iodide or water-soluble 1-ethyl-(3,3-dimethylaminopropyl)carbodiimide. J Biomater Sci Polym Ed 15(6):767–780. https://doi.org/10.1163/156856204774196153

    Article  CAS  PubMed  Google Scholar 

  137. Wang C, Yan Q, Liu H-B, Zhou X-H, Xiao S-J (2011) Different EDC/NHS activation mechanisms between PAA and PMAA brushes and the following Amidation reactions. Langmuir 27(19):12058–12068. https://doi.org/10.1021/la202267p

    Article  CAS  PubMed  Google Scholar 

  138. Hoare DG, Koshland DE (1967) A method for the quantitative modification and estimation of carboxylic acid groups in proteins. J Biol Chem 242(10):2447–2453

    CAS  PubMed  Google Scholar 

  139. Larsson P-O, Mosbach K (1971) Preparation of a NAD(H)-polymer matrix showing coenzymic function of the bound pyridine nucleotide. Biotechnol Bioeng 13(3):393–398. https://doi.org/10.1002/bit.260130306

    Article  CAS  PubMed  Google Scholar 

  140. Lowe CR, Harvey MJ, Craven DB, Dean PDG (1973) Some parameters relevant to affinity chromatography on immobilized nucleotides. Biochem J 133(3):499–506. https://doi.org/10.1042/bj1330499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Staros JV (1982) N-hydroxysulfosuccinimide active esters: bis(N-hydroxysulfosuccinimide) esters of two dicarboxylic acids are hydrophilic, membrane-impermeant, protein cross-linkers. Biochemistry 21(17):3950–3955. https://doi.org/10.1021/bi00260a008

    Article  CAS  PubMed  Google Scholar 

  142. Khalfan H, Abuknesha R, Rand-Weaver M, Price RG, Robinson D (1986) Aminomethyl coumarin acetic acid: a new fluorescent labelling agent for proteins. Histochem J 18(9):497–499. https://doi.org/10.1007/bf01675617

    Article  CAS  PubMed  Google Scholar 

  143. Hermanson GT (2013) Chapter 10 - fluorescent probes. In: Bioconjugate techniques, 3rd edn. Academic Press, Boston, pp 395–463. https://doi.org/10.1016/B978-0-12-382239-0.00010-8

    Chapter  Google Scholar 

  144. Harvey DJ (2011) Derivatization of carbohydrates for analysis by chromatography; electrophoresis and mass spectrometry. J Chromatogr B 879(17–18):1196–1225. https://doi.org/10.1016/j.jchromb.2010.11.010

    Article  CAS  Google Scholar 

  145. Nakano M, Kakehi K, Taniguchi N, Kondo A (2011) Capillary electrophoresis and capillary electrophoresis–mass spectrometry for structural analysis of N-Glycans derived from glycoproteins. In: Volpi N (ed) Capillary electrophoresis of carbohydrates: from Monosaccharides to complex polysaccharides. Humana Press, Totowa, NJ, pp 205–235. https://doi.org/10.1007/978-1-60761-875-1_9

    Chapter  Google Scholar 

  146. Gibrat C, Cicchetti F (2011) Potential of cystamine and cysteamine in the treatment of neurodegenerative diseases. Prog Neuro-Psychopharmacol Biol Psychiatry 35(2):380–389. https://doi.org/10.1016/j.pnpbp.2010.11.023

    Article  CAS  Google Scholar 

  147. Fujisawa T, Rubin B, Suzuki A, Patel PS, Gahl WA, Joshi BH, Puri RK (2012) Cysteamine suppresses invasion, metastasis and prolongs survival by inhibiting matrix Metalloproteinases in a mouse model of human pancreatic Cancer. PLoS One 7(4):e34437. https://doi.org/10.1371/journal.pone.0034437

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Brunelli C, Amici C, Angelini M, Fracassi C, Belardo G, Santoro MG (2012) The non-steroidal anti-inflammatory drug indomethacin activates the eIF2alpha kinase PKR, causing a translational block in human colorectal cancer cells. Biochem J 443(2):379–386. https://doi.org/10.1042/bj20111236

    Article  CAS  PubMed  Google Scholar 

  149. Suh W, Chung JK, Park SH, Kim SW (2001) Anti-JL1 antibody-conjugated poly (L-lysine) for targeted gene delivery to leukemia T cells. J Control Release 72(1–3):171–178

    Article  CAS  PubMed  Google Scholar 

  150. Toni R, Mirandola P, Gobbi G, Vitale M (2007) Neuroendocrine regulation and tumor immunity. Eur J Histochem 51(Suppl 1):133–138

    PubMed  Google Scholar 

  151. Shadidi M, Sioud M (2003) Selective targeting of cancer cells using synthetic peptides. Drug Resist Updat 6(6):363–371

    Article  CAS  PubMed  Google Scholar 

  152. Benns JM, Maheshwari A, Furgeson DY, Mahato RI, Kim SW (2001) Folate-PEG-folate-graft-polyethylenimine-based gene delivery. J Drug Target 9(2):123–139

    Article  CAS  PubMed  Google Scholar 

  153. Hong G, Yuan R, Liang B, Shen J, Yang X, Shuai X (2008) Folate-functionalized polymeric micelle as hepatic carcinoma-targeted, MRI-ultrasensitive delivery system of antitumor drugs. Biomed Microdevices 10(5):693–700. https://doi.org/10.1007/s10544-008-9180-9

    Article  CAS  PubMed  Google Scholar 

  154. Low PS, Antony AC (2004) Folate receptor-targeted drugs for cancer and inflammatory diseases. Adv Drug Deliv Rev 56(8):1055–1058. https://doi.org/10.1016/j.addr.2004.02.003

    Article  CAS  PubMed  Google Scholar 

  155. Liang B, He ML, Xiao ZP, Li Y, Chan CY, Kung HF, Shuai XT, Peng Y (2008) Synthesis and characterization of folate-PEG-grafted-hyperbranched-PEI for tumor-targeted gene delivery. Biochem Biophys Res Commun 367(4):874–880. https://doi.org/10.1016/j.bbrc.2008.01.024

    Article  CAS  PubMed  Google Scholar 

  156. Gabizon A, Horowitz AT, Goren D, Tzemach D, Mandelbaum-Shavit F, Qazen MM, Zalipsky S (1999) Targeting folate receptor with folate linked to extremities of poly(ethylene glycol)-grafted liposomes: in vitro studies. Bioconjug Chem 10(2):289–298. https://doi.org/10.1021/bc9801124

    Article  CAS  PubMed  Google Scholar 

  157. Yoo HS, Park TG (2004) Folate receptor targeted biodegradable polymeric doxorubicin micelles. J Control Release 96(2):273–283. https://doi.org/10.1016/j.jconrel.2004.02.003

    Article  CAS  PubMed  Google Scholar 

  158. Hwa Kim S, Hoon Jeong J, Chul Cho K, Wan Kim S, Gwan Park T (2005) Target-specific gene silencing by siRNA plasmid DNA complexed with folate-modified poly(ethylenimine). J Control Release 104(1):223–232. https://doi.org/10.1016/j.jconrel.2005.02.006

    Article  CAS  PubMed  Google Scholar 

  159. Cudaj M, Cudaj J, Hofe T, Luy B, Wilhelm M, Guthausen G (2012) Polystyrene solutions: characterization of molecular motional modes by spectrally resolved low- and high-field NMR relaxation. Macromol Chem Phys 213(17):1833–1840. https://doi.org/10.1002/macp.201200092

    Article  CAS  Google Scholar 

  160. Rule GS, Hitchens TK (2006) Fundamentals of protein NMR spectroscopy. In: Focus on Structural Biology, vol 5. Springer Netherlands, p 532. https://doi.org/10.1007/1-4020-3500-4

  161. Jain A, Cheng K (2017) The principles and applications of avidin-based nanoparticles in drug delivery and diagnosis. J Control Release 245:27–40. https://doi.org/10.1016/j.jconrel.2016.11.016

    Article  CAS  PubMed  Google Scholar 

  162. Wilchek M, Bayer EA, Livnah O (2006) Essentials of biorecognition: the (strept)avidin-biotin system as a model for protein-protein and protein-ligand interaction. Immunol Lett 103(1):27–32. https://doi.org/10.1016/j.imlet.2005.10.022

    Article  CAS  PubMed  Google Scholar 

  163. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28(1):235–242. https://doi.org/10.1093/nar/28.1.235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Diamandis EP, Christopoulos TK (1991) The biotin-(strept)avidin system: principles and applications in biotechnology. Clin Chem 37(5):625–636

    CAS  PubMed  Google Scholar 

  165. Tausig F, Wolf FJ (1964) Streptavidin—A substance with avidin-like properties produced by microorganisms. Biochem Biophys Res Commun 14(3):205–209. https://doi.org/10.1016/0006-291X(64)90436-X

    Article  CAS  PubMed  Google Scholar 

  166. Dundas CM, Demonte D, Park S (2013) Streptavidin-biotin technology: improvements and innovations in chemical and biological applications. Appl Microbiol Biotechnol 97(21):9343–9353. https://doi.org/10.1007/s00253-013-5232-z

    Article  CAS  PubMed  Google Scholar 

  167. Hendrickson WA, Pahler A, Smith JL, Satow Y, Merritt EA, Phizackerley RP (1989) Crystal structure of core streptavidin determined from multiwavelength anomalous diffraction of synchrotron radiation. Proc Natl Acad Sci U S A 86(7):2190–2194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Huberman T, Eisenberg-Domovich Y, Gitlin G, Kulik T, Bayer EA, Wilchek M, Livnah O (2001) Chicken avidin exhibits pseudo-catalytic properties: biochemical, structural, and electrostatic consequences. J Biol Chem 276(34):32031–32039. https://doi.org/10.1074/jbc.M102018200

    Article  CAS  PubMed  Google Scholar 

  169. Schechter B, Silberman R, Arnon R, Wilchek M (1990) Tissue distribution of avidin and streptavidin injected to mice. Effect of avidin carbohydrate, streptavidin truncation and exogenous biotin. Eur J Biochem 189(2):327–331

    Article  CAS  PubMed  Google Scholar 

  170. Nguyen TT, Sly KL, Conboy JC (2012) Comparison of the energetics of avidin, streptavidin, neutrAvidin, and anti-biotin antibody binding to biotinylated lipid bilayer examined by second-harmonic generation. Anal Chem 84(1):201–208. https://doi.org/10.1021/ac202375n

    Article  CAS  PubMed  Google Scholar 

  171. Chen S, Zhao X, Chen J, Chen J, Kuznetsova L, Wong SS, Ojima I (2010) Mechanism-based tumor-targeting drug delivery system. Validation of efficient vitamin receptor-mediated endocytosis and drug release. Bioconjug Chem 21(5):979–987. https://doi.org/10.1021/bc9005656

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Ma M, Yuan ZF, Chen XJ, Li F, Zhuo RX (2012) A facile preparation of novel multifunctional vectors by non-covalent bonds for co-delivery of doxorubicin and gene. Acta Biomater 8(2):599–607. https://doi.org/10.1016/j.actbio.2011.11.006

    Article  CAS  PubMed  Google Scholar 

  173. Scott Wilbur D, Pathare PM, Hamlin DK, Stayton PS, To R, Klumb LA, Buhler KR, Vessella RL (1999) Development of new biotin/streptavidin reagents for pretargeting. Biomol Eng 16(1–4):113–118. https://doi.org/10.1016/S1050-3862(99)00044-3

    Article  Google Scholar 

  174. Arribillaga L, Durantez M, Lozano T, Rudilla F, Rehberger F, Casares N, Villanueva L, Martinez M, Gorraiz M, Borras-Cuesta F, Sarobe P, Prieto J, Lasarte JJ (2013) A fusion protein between streptavidin and the endogenous TLR4 ligand EDA targets Biotinylated antigens to dendritic cells and induces T cell responses in vivo. Biomed Res Int 2013:9. https://doi.org/10.1155/2013/864720

    Article  Google Scholar 

  175. Petronzelli F, Pelliccia A, Anastasi AM, Lindstedt R, Manganello S, Ferrari LE, Albertoni C, Leoni B, Rosi A, D’Alessio V, Deiana K, Paganelli G, De Santis R (2010) Therapeutic use of avidin is not hampered by antiavidin antibodies in humans. Cancer Biother Radiopharm 25(5):563–570. https://doi.org/10.1089/cbr.2010.0797

    Article  CAS  PubMed  Google Scholar 

  176. Ren WX, Han J, Uhm S, Jang YJ, Kang C, Kim J-H, Kim JS (2015) Recent development of biotin conjugation in biological imaging, sensing, and target delivery. Chem Commun 51(52):10403–10418. https://doi.org/10.1039/c5cc03075g

    Article  CAS  Google Scholar 

  177. Muggia FM (1998) Doxil in breast cancer. J Clin Oncol 16(2):811–812. https://doi.org/10.1200/JCO.1998.16.2.811

    Article  CAS  PubMed  Google Scholar 

  178. Porche DJ (1996) Liposomal doxorubicin (Doxil). J Assoc Nurses AIDS Care 7(2):55–59. https://doi.org/10.1016/S1055-3290(96)80016-1

    Article  CAS  PubMed  Google Scholar 

  179. Tagami T, Ozeki T (2017) Recent trends in clinical trials related to carrier-based drugs. J Pharm Sci 106(9):2219–2226. https://doi.org/10.1016/j.xphs.2017.02.026

    Article  CAS  PubMed  Google Scholar 

  180. Cagel M, Tesan FC, Bernabeu E, Salgueiro MJ, Zubillaga MB, Moretton MA, Chiappetta DA (2017) Polymeric mixed micelles as nanomedicines: achievements and perspectives. Eur J Pharm Biopharm 113:211–228. https://doi.org/10.1016/j.ejpb.2016.12.019

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt

    Perihan Elzahhar & Ahmed S. F. Belal

  2. Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt

    Fatema Elamrawy & Nada A. Helal

  3. Department of Pharmaceutical Sciences, School of Pharmacy & Physician Assistant Studies (SOPPAS), University of Saint Joseph (USJ), Hartford, CT, USA

    Mohamed Ismail Nounou

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    Volkmar Weissig

  2. Nanomedicine Center of Excellence in Translational Cancer Research, Midwestern University, Glendale, AZ, USA

    Tamer Elbayoumi

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Elzahhar, P., Belal, A.S.F., Elamrawy, F., Helal, N.A., Nounou, M.I. (2019). Bioconjugation in Drug Delivery: Practical Perspectives and Future Perceptions. In: Weissig, V., Elbayoumi, T. (eds) Pharmaceutical Nanotechnology. Methods in Molecular Biology, vol 2000. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9516-5_11

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  • DOI: https://doi.org/10.1007/978-1-4939-9516-5_11

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9515-8

  • Online ISBN: 978-1-4939-9516-5

  • eBook Packages: Springer Protocols

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