Methotrexate-loaded PEGylated gold nanoparticles as hemocompatible and pH-responsive anticancer drug nanoconjugate

Methotrexate (MTX) is a well-known chemotherapeutic agent for solid tumor. However, its clinical usage is limited due to low permeability, cellular drug efflux, and non-specific drug delivery. These constraints require dose dumping and result in dose-dependent toxic effects. In the current study, MT...

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Bibliographic Details
Published in:Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology 2021-08, Vol.23 (8), Article 195
Main Authors: Rahman, Mehreen, Khan, Jamshaid Ali, Kanwal, Ummarah, Awan, Uzma Azeem, Raza, Abida
Format: Article
Language:English
Subjects:
Anticancer properties
Antitumor activity
Antitumor agents
Cancer
Characterization and Evaluation of Materials
Chemisorption
Chemistry and Materials Science
Citric acid
Cytotoxicity
Deactivation
Dicarboxylic acids
Drug delivery
Drug dosages
Dumping
Efflux
Gold
Inorganic Chemistry
Lasers
Materials Science
Methotrexate
MPEG encoders
Muscles
Nanoparticles
Nanotechnology
Optical Devices
Optics
Permeability
pH effects
Photonics
Physical Chemistry
Polyethylene glycol
Research Paper
Rhabdomyosarcoma
Skeletal muscle
Solid tumors
Stability
Toxicity
Tumors
Zeta potential
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Summary:Methotrexate (MTX) is a well-known chemotherapeutic agent for solid tumor. However, its clinical usage is limited due to low permeability, cellular drug efflux, and non-specific drug delivery. These constraints require dose dumping and result in dose-dependent toxic effects. In the current study, MTX-loaded PEGylated gold nanoparticles (PEG-MTX-AuNPs) exposed to acidic pH (tumor cell) trigger a significant drug release profile. MTX was conjugated to citrate functionalized AuNP and stabilized by thiolated methyl polyethylene glycol (mPEG-SH). PEG-MTX-AuNP was cationic with 39.5 ± 1.2 mV zeta potential and a particle size of 39 nm, as revealed by DLS and TEM. AuNP size ranging from 40 to 50 nm was favorable for maximum endosomal uptake and fast drug release. MTX-AuNP showed 39.4% (22.28 µg/ml) drug loading efficiency. Spectroscopic examinations confirmed MTX chemisorption onto AuNPs via carboxyl (–COOH) and gold dative bond. In vitro release study indicated a 6.5-fold increased MTX release in the acidic environment (pH 4.5) compared to physiological pH. The terminal mPEG provided stability in a biological medium, refrained from protein deactivation, and exhibited significant hemocompatibility (less than 5% hemolysis up to 10 μM concentration). In vitro cytotoxicity against human rhabdomyosarcoma (RD) cells indicated significant ( p  
ISSN:1388-0764
1572-896X
DOI:10.1007/s11051-021-05296-0