Targeted delivery of paclitaxel-loaded recombinant α-fetoprotein fragment-conjugated nanoparticles to tumor cells

Godovannyi, A. V.; Vorontsov, E. A.; Gukasova, N. V.; Pozdnyakova, N. V.; Vasilenko, E. A.; Yabbarov, N. G.; Dubovik, E. G.; Северин, С. Е.; Северин, Е. С.; Гнучев, Н. В.

doi:10.1134/s160767291104003x

Cited by 10 publications

(12 citation statements)

References 2 publications

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“…The AFP-CD-DOX conjugate could potentially bind to SR identified sites on AFP-CD between AAs #480-530 in the present report. Further examples of published AFP-CD drug delivery cargos directed against ovarian and breast cancers could include: (a) AFP-CD fragments fused to a sequence of 22 glutamic acid residues [76]; (b) an RNA aptamer bound to AFP-CD [77]; (c) AFP-CD segments conjugated to paclitaxel-loaded nanoparticles [17] and (d) AFP-CD segments conjugated to oligocationic homologs of nuclear localization signals capable of binding single/double oligonucleotides [78]. Secondly, AFP-CD SR/SAR sequences could be used as targeting components of drug delivery systems to improve drug selectivity and to overcome multidrug resistance resulting from ABC-transporter activation [79].…”

Section: Potential Biomedical and Pharmaceutical Applications For Sr/mentioning

confidence: 99%

“…However, isolated reports of other receptors and binding proteins for AFP have emerged in the literature throughout the last several decades; these include G-coupled chemokine receptors, immune/inflammatory cell receptors, NK receptors and intra-cytoplasmic retinoic acid receptors [12][13][14]. In the last several years, the C-terminal (CD) third domain of HAFP has been identified and confirmed as a receptor binding fragment whose recombinant product shows promise for selective delivery of anti-cancer agents such as doxorubricin [15][16][17]. Studies of recombinant HAFP-CD have demonstrated efficiency of expression, high-purification yields, and recoverable protein fragment-folding capabilities [18,19].…”

Section: Introductionmentioning

confidence: 99%

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The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets

2015

Journal of Drug Targeting

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Recent studies have demonstrated that the carboxyterminal third domain of alpha-fetoprotein (AFP-CD) binds with various ligands and receptors. Reports within the last decade have established that AFP-CD contains a large fragment of amino acids that interact with several different receptor types. Using computer software specifically designed to identify protein-to-protein interaction at amino acid sequence docking sites, the computer searches identified several types of scavenger-associated receptors and their amino acid sequence locations on the AFP-CD polypeptide chain. The scavenger receptors (SRs) identified were CD36, CD163, Stabilin, SSC5D, SRB1 and SREC; the SR-associated receptors included the mannose, low-density lipoprotein receptors, the asialoglycoprotein receptor, and the receptor for advanced glycation endproducts (RAGE). Interestingly, some SR interaction sites were localized on the AFP-derived Growth Inhibitory Peptide (GIP) segment at amino acids #480-500. Following the detection studies, a structural subdomain analysis of both the receptor and the AFP-CD revealed the presence of epidermal growth factor (EGF) repeats, extracellular matrix-like protein regions, amino acid-rich motifs and dimerization subdomains. For the first time, it was reported that EGF-like sequence repeats were identified on each of the three domains of AFP. Thereafter, the localization of receptors on specific cell types were reviewed and their functions were discussed.

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Section: Potential Biomedical and Pharmaceutical Applications For Sr/mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets

2015

Journal of Drug Targeting

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“…Previous studies have shown the efficiency of rhAFP3d as a vector in the macromolecule architectures that can selectively target cancer cells [4, 5]. Based on the rhAFP3d sequence, we obtained a chimeric protein named ApE1, with a higher content of carboxyl groups that can be used for covalent attachment of anticancer drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Human alpha -fetoprotein (AFP) comprises three domains; the third domain is responsible for binding to the cell surface of many cancer types [2]. Our previous work yielded promising results concerning the use of the recombinant third domain of human alpha -fetoprotein (rhAFP3d) as a vector in architectures for targeted drug delivery [3–5]. Small rhAFP3d peptide fragments are also currently being investigated∗∗.…”

Section: Introductionmentioning

confidence: 99%

“…To overcome this limitation, two approaches were employed; one of them involving drug-loaded rhAFP3d-conjugated nanoparticles [5], and the other one using recombinant technologies to obtain a new rhAFP3d-based protein vector with increased number of reactive groups. The new vector protein was constructed based on the amino acid sequence of rhAFP3d with receptor-binding activity fused to a C-terminal fragment of 22 glutamic acid residues (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

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New Protein Vector ApE1 for Targeted Delivery of Anticancer Drugs

Позднякова

Gorokhovets

Gukasova

et al. 2012

Journal of Biomedicine and Biotechnology

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A new chimeric gene ApE1 encoding the receptor-binding domain of the human alpha-fetoprotein fused to a sequence of 22 glutamic acid residues was constructed. A new bacterial producer strain E. coli SHExT7 ApE1 was selected for ApE1 production in a soluble state. A simplified method was developed to purify ApE1 from bacterial biomass. It was shown that the new vector protein selectively interacts with AFP receptors on the tumor cell surface and can be efficiently accumulated in tumor cells. In addition, ApE1 was shown to be stable in storage and during its chemical modification. An increased number of carboxyl groups in the molecule allows the production of cytotoxic compound conjugates with higher drug-loading capacity and enhanced tumor targeting potential.

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Alpha-fetoprotein: a renaissance

2013

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Alpha-fetoprotein (AFP) is a major mammalian embryo-specific and tumor-associated protein that is also present in small quantities in adults at normal conditions. Discovery of the phenomenon of AFP biosynthesis in carcinogenesis by G. Abelev and Yu. Tatarinov 50 years ago, in 1963, provoked intensive studies of this protein. AFPs of some mammalian species were isolated, purified and physico-chemically and immunochemically characterized. Despite the significant success in study of AFP, its three-dimensional structure, mechanisms of receptor binding along with a structure of the receptor itself and, what is the most important, its biological role in embryo- and carcinogenesis remain still obscure. Due to difficulties linked with methodological limitations, research of AFP was to some extent extinguished by the 1990 s. However, over the last decade a growing number of investigations of AFP and its usage as a tumor-specific biomarker have been observed. This was caused by the use of new technologies, primarily, computer-based and genetic engineering approaches in studying of this very important oncodevelopmental protein. Our review summarizes efforts of different scientific groups throughout the world in studying AFP for 50 years with emphasis on detailed description of recent achievements in this field.

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Targeted delivery of paclitaxel-loaded recombinant α-fetoprotein fragment-conjugated nanoparticles to tumor cells

Cited by 10 publications

References 2 publications

The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets

The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets

New Protein Vector ApE1 for Targeted Delivery of Anticancer Drugs

Alpha-fetoprotein: a renaissance

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