The Principles and Applications of Avidin-Based Nanoparticles in Drug Delivery and Diagnosis
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Journal of Controlled Release 245 (2017) 27–40 Contents lists available at ScienceDirect Journal of Controlled Release journal homepage: www.elsevier.com/locate/jconrel Review article The principles and applications of avidin-based nanoparticles in drug delivery and diagnosis Akshay Jain, Kun Cheng ⁎ Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri Kansas City, Kansas City, MO 64108, United States article info abstract Article history: Avidin-biotin interaction is one of the strongest non-covalent interactions in the nature. Avidin and its analogues Received 7 October 2016 have therefore been extensively utilized as probes and affinity matrices for a wide variety of applications in bio- Accepted 7 November 2016 chemical assays, diagnosis, affinity purification, and drug delivery. Recently, there has been a growing interest in Available online 16 November 2016 exploring this non-covalent interaction in nanoscale drug delivery systems for pharmaceutical agents, including small molecules, proteins, vaccines, monoclonal antibodies, and nucleic acids. Particularly, the ease of fabrication Keywords: Nanotechnology without losing the chemical and biological properties of the coupled moieties makes the avidin-biotin system a Avidin versatile platform for nanotechnology. In addition, avidin-based nanoparticles have been investigated as Neutravidin diagnostic systems for various tumors and surface antigens. In this review, we will highlight the various Streptavidin fabrication principles and biomedical applications of avidin-based nanoparticles in drug delivery and diagnosis. Non-covalent interaction The structures and biochemical properties of avidin, biotin and their respective analogues will also be discussed. Drug delivery © 2016 Elsevier B.V. All rights reserved. Imaging Diagnosis Contents 1. Introduction............................................................... 27 2. Biochemicalinsightsofavidin,biotinandanalogues............................................. 29 2.1. Structureandphysical-chemicalpropertiesofavidin......................................... 29 2.2. Avidinanalogues.......................................................... 29 2.3. Biotinandanalogues........................................................ 29 3. Applicationsinnanoscaledeliverysystems................................................. 29 3.1. Nucleicaciddelivery........................................................ 29 3.2. Proteinandpeptidedelivery.................................................... 31 3.3. Vaccinedelivery.......................................................... 31 3.4. Monoclonalantibody(MAb)delivery................................................ 32 3.5. Smallmoleculedelivery...................................................... 33 4. Applicationsofnanoscaleavidinsystemsindiagnosisandbiotechnology.................................... 33 4.1. Surfaceantigendetection...................................................... 33 4.2. Imaginganddiagnosis....................................................... 34 4.3. Tissueengineering......................................................... 36 5. Conclusion................................................................ 37 Acknowledgment............................................................... 37 References.................................................................. 37 1. Introduction ⁎ Corresponding author at: Division of Pharmaceutical Sciences, School of Pharmacy, Nanotechnology holds the greatest potential and promise for bio- University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO 64108, United fi States. medical research. Signi cant progress has been achieved in nanotech- E-mail address: [email protected] (K. Cheng). nology across a wide spectrum of fields from applied physics to http://dx.doi.org/10.1016/j.jconrel.2016.11.016 0168-3659/© 2016 Elsevier B.V. All rights reserved. 28 A. Jain, K. Cheng / Journal of Controlled Release 245 (2017) 27–40 biotechnology to medicine. Naturally occurring interactions are the crux especially biochemical assays and affinity purification, over four de- for such innovations and have been explored for various nanoscale cades. Tremendous efforts have also been converged to utilize the in- applications to achieve uncountable scientific goals. As one of the stron- herent properties of avidin in biotechnology medicines, and some of gest non-covalent interactions in the nature, the avidin-biotin interac- them have been evaluated in clinical studies. Recently, the avidin-biotin tion has been utilized in nanoscale drug delivery systems for technology underwent a renaissance in nanoscale drug delivery and di- pharmaceutical agents, including small molecules, proteins, vaccines, agnostics. Targeting ligands or imaging agents can be easily coupled to monoclonal antibodies, and nucleic acids (Fig. 1). nanocarriers via the avidin-biotin linkage. For example, PMA hydrogel Avidin is a basic tetrameric glycoprotein composed of four identi- capsule functionalized with biotin forms a stable nanocomplex with av- cal subunits, each binds to biotin with high specificity and affinity idin-coupled antibodies and improved its cellular uptake in cancer cells −15 (Kd ~10 M). Avidin is originally derived from the eggs of aves, [7]. Liposomes modified with biotinylated polyethylene glycol can at- reptiles and amphibians. Avidin-biotin interaction is considered tract a layer of neutravidin on the surface to resist nonspecificbinding one of the most specific and stable non-covalent interactions, to serum proteins, thus leading to prolonged circulation time [8]. which is about 103 to 106 times higher than an antigen-antibody in- Microbubbles coupled with RGD peptide via avidin-biotin linkage teraction [1]. Several genetically and chemically engineered avidin were developed for the detection of Hep-2 related tumor angiogenesis and its analogues have been studied to improve the functional and [9]. Neutravidin conjugated superparamagnetic iron oxide nanoparticle structural characteristics of avidins [2]. The biggest advantage of has also been explored as an imaging agent for rhodopsin degeneration this system is its high affinity interaction, which is robust and stable [10]. More recently, the avidin-based nanotechnology has found its ap- against manipulation, proteolytic enzymes, temperature, pH, harsh plications in tissue engineering and cellular regeneration [11,12].Inone organic reagents, and other denaturing reagents [3–6]. Therefore, such study, an avidin-biotin system was used to improve osteoblast-like the avidin-biotin interaction serves as a great tool in the biomedical cell adhesion to a highly porous calcium phosphate glass scaffold for and nanotechnological applications. On the other hand, biotin-based bone tissue engineering [12]. conjugates are easy to synthesize and have less impact on the activ- The aim of this review is to highlight the unprecedented advantages ity of the biomolecules. of avidin and its analogues in nanotechnology. We will critically evalu- Compared to other covalent and non-covalent interactions, the avi- ate a wide variety of applications that have been recently explored for din-biotin system provides enormous advantages such as amplification drug delivery and diagnosis. It is our hope that this review will serve of weak signals, efficient operation, robust stability. Therefore, avidin as a one-stop reference for investigators who are interested in exploring has been a very versatile modality in the field of biotechnology, the avidin-based nanotechnology in their fields. Avidin Fig. 1. Avidin-based nanoscale systems in various applications. A. Jain, K. Cheng / Journal of Controlled Release 245 (2017) 27–40 29 2. Biochemical insights of avidin, biotin and analogues biotinylated moieties and biotin-coated surfaces for the detection of protein-specificantibodies[36]. 2.1. Structure and physical-chemical properties of avidin Bradavidin II is a relatively new avidin analogue that was isolated from Bradyrhizobium japonicum, a nitrogen-fixing bacteria found in Avidin is a basic (pI ~10), highly stable, tetrameric glycoprotein the root nodules of the soybean plant [37].BradavidinIIshowsamod- (molecular weight 66–69 kDa) that contains terminal N-acetyl glucos- erate amino acid similarity with avidin (38%) and streptavidin (32%), amine and mannose moieties [13]. Each of the four subunits contains but exhibits the same biotin binding affinity as avidin. Compared to 128 amino acids and binds to biotin with high specificity and affinity streptavidin, bradavidin II could be a better choice for therapeutic −15 (Kd ~10 M) [14,15]. The subunit is composed of eight antiparallel applications because it is less immunogenic. The physical-chemical β-strands that form a β-barrel, whose wide end binds to biotin [16]. properties of avidin, neutravidin, streptavidin and bradavidin are sum- The avidin-biotin interaction is approximately 103 to 106 times higher marized in Table 1. than an antibody-antigen interaction. However, avidin may have a Most of the avidin analogues have a similar tetrameric structure, high degree of nonspecificbindingin vivo due to its basic pI and glyco- which is beneficial to high amplification of a desired signal. On the sylation. Rigorous efforts have been made to study the structural prop- other hand, the tetrameric assembly may affect the accuracy of binding erties of avidin using X-ray analysis of its 3D structure to improve its quantitation due to the uncertainty of the precise binding stoichiometry