α1-Acid Glycoprotein Has the Potential to Serve as a Biomimetic Drug Delivery Carrier for Anticancer Agents

Matsusaka, Kotaro; Ishima, Yu; Maeda, Hitoshi; Kinoshita, Ryô; Ichimizu, Shota; Taguchi, Kazuaki; Chuang, Victor Tuan Giam; Nishi, Koji; Yamasaki, Keishi; Otagiri, Masaki; Watanabe, Hiroshi; Maruyama, Toru

doi:10.1016/j.xphs.2019.07.002

Cited by 5 publications

(2 citation statements)

References 38 publications

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“…Serum protein binding is important not only for arginine-rich CPPs but also for other drugs to determine their in vivo fate; however, only a few proteins such as albumin and AGP have been studied. 39 Our study demonstrates that Hpx can be a binding protein in serum of arginine-rich CPPs and their conjugates with drugs. Hpx has high affinity to heme and is involved in scavenging free heme in plasma, a potentially toxic species.…”

Section: ■ Results and Discussionmentioning

confidence: 66%

“…Although the importance of arginine-rich CPPs as a means of drug delivery and the effects of serum protein binding have been described, information on their exact binding partner in serum is limited. Serum protein binding is important not only for arginine-rich CPPs but also for other drugs to determine their in vivo fate; however, only a few proteins such as albumin and AGP have been studied . Our study demonstrates that Hpx can be a binding protein in serum of arginine-rich CPPs and their conjugates with drugs.…”

Section: Resultsmentioning

confidence: 78%

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Hemopexin as a Potential Binding Partner of Arginine-Rich Cell-Penetrating Peptides in Serum

Nomura

Kawano

Kawaguchi

et al. 2022

ACS Pharmacol. Transl. Sci.

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Serum proteins affect the in vivo fate and cellular uptake of arginine-rich cell-penetrating peptides (CPPs) and drugs delivered by CPPs. Although the binding of CPPs to serum proteins may possibly reduce their cellular uptake to some extent, it may also prolong their circulation half-life in vivo. We aimed to identify novel binding proteins of arginine-rich CPPs in serum to better understand their in vivo fate and develop more sophisticated drug delivery systems using CPPs. Isothermal titration calorimetry analysis suggests that albumin, the most abundant protein in serum, binds to D-forms of oligoarginine; however, the dissociation constants are several tens of a micromolar. Candidate proteins with the potential of binding to arginine-rich CPPs in serum were then explored using nondenaturing polyacrylamide gel electrophoresis followed by mass spectrometry analysis. Studies using fluorescence correlation spectroscopy determined hemopexin as a potential binding partner of D-forms of arginine-rich CPPs, including D-octaarginine (r 8 ) and the D-form of the peptide, corresponding to HIV-1 Rev (34−50), with dissociation constants of submicromolar to micromolar range. Using flow cytometry and a split-luciferase-based system, the promotion effect of hemopexin on the total cellular uptake and cytosolic localization of cargos conjugated with these CPPs was confirmed. Therefore, this study elucidated hemopexin as a potential binding partner of D-arginine-rich CPPs that may affect their in vivo fate and cellular uptake.

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Section: ■ Results and Discussionmentioning

confidence: 66%

Section: Resultsmentioning

confidence: 78%