Protein-drug nanoconjugates: Finding the alternative proteins as drug carrier.
Present study was conducted to establish the interaction of bovine fetuin-A to validate its binding modalities with doxorubicin (Dox). Fetuin-A was purified to highest purity and monodispersity. Green synthesis of fetuin-A conjugated gold nanoparticles (F-GNPs) has been performed giving typical UV-maxima with subtle variation in fourier transform infrared spectroscopy (FTIR). Atomic force microscopy (AFM) revealed spherical shaped, polydisperse F-GNPs of varying sizes, complementing the radius of hydration (19.5-62.4nm) by dynamic light scattering (DLS). Circular dichroism (CD) analysis of fetuin-A with respect to Dox interaction shows remarkable reduction in ellipticity with increasing concentrations of Dox (20-120μM). Fetuin-A:Dox and F-GNPs:Dox at variable concentrations revealed significantly enhanced absorption spectra, while a continuous decrease in florescence (560nm). This effect was more drastic when Dox interact with fetuin-A as compared to F-GNPs. Some known antimicrobial drugs were also investigated under similar conditions, giving strong quenching effect in a dose dependent manner suggesting the significant yet differential interactions. In cytotoxicity assay, fetuin-A:Dox conjugates revealed less toxicity as compared to F-GNPs:Dox and Dox alone. In-silico studies of the fetuin-A:Dox complex suggest that the drug binds in the major grove between beta-sheet and long loop region of D1 domain and stabilized by several hydrogen bonds.
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, 75270, Pakistan. Electronic address: iqramunir2010@hotmail.com.
Iqra
I
Munir
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, 75270, Pakistan. Electronic address: sadiaajmalkhan@gmail.com.
Sadia
S
Ajmal
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, 75270, Pakistan. Electronic address: raza_shahm@yahoo.com.
Muhammad Raza
MR
Shah
School of Pharmacy, Chapman University, 9401 Jeronimo Road, Irvine, CA, 92618, USA. Electronic address: aahmed@chapman.edu.
Aftab
A
Ahmad
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, 75270, Pakistan. Electronic address: abdul_hameed8@hotmail.com.
Abdul
A
Hameed
H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, 75270, Pakistan. Electronic address: abid.ali@iccs.edu.
Syed Abid
SA
Ali
D000818:Animals; D002417:Cattle; D004317:Doxorubicin / Q000737:chemistry* / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D006046:Gold / Q000737:chemistry; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D053768:Metal Nanoparticles / Q000737:chemistry; D062105:Molecular Docking Simulation; D058726:Nanoconjugates / Q000737:chemistry*; D011487:Protein Conformation; D055550:Protein Stability / Q000187:drug effects; D012492:Salts / Q000494:pharmacology; D060749:alpha-2-HS-Glycoprotein / Q000737:chemistry* / Q000378:metabolism
D004337:Drug Carriers; D058726:Nanoconjugates; D012492:Salts; D060749:alpha-2-HS-Glycoprotein; D006046:Gold; D004317:Doxorubicin
Antibiotics; Bioconjugates; Bovine fetuin-A; Circular dichroism; Doxorubicin; Gold- nanoparticles