Methoxy poly (ethylene glycol)-block-poly (glutamic acid)-graft-6-(2-nitroimidazole) hexyl amine nanoparticles for potential hypoxia-responsive delivery of doxorubicin.
Tumor microenvironment-responsive nano drug delivery vehicles are gaining mounting attention in the field of biomedical sciences. The hypoxic response of the tumorous cells due to very low partial pressure of oxygen (some time less than 2.5 mm of Hg) in the tumor tissues makes hypoxia-responsive drug delivery system as the more appealing in cancer chemotherapy. Based on these considerations, we synthesized hypoxia-responsive polymeric materials methoxy poly (ethylene glycol)-block-poly (glutamic acid)-graft-6-(2-nitroimidazole) hexyl amine (mPEG-b-PLG-g-NID) by conjugation of the hydrophobic nitro imidazole derivative (NID)[6-(2-nitroimidazole) hexyl amine] with the pendant carboxylic group of poly (ethylene glycol)-block-poly (L-glutamic acid)(mPEG-b-PLG). The structure and degree of substitution were confirmed by proton NMR, FTIR, and UV-Vis spectroscopy. The degree of substitution was found to enhance with the increase in NID to polymer ratio. The hypoxia response of the material was evaluated by UV-Vis spectroscopy and zeta potential measurements. Doxorubicin was hydrophobically encapsulated in the micellar core of the hypoxia-responsive nanoparticles. The drug-loaded micelles showed faster release in hypoxic condition as compared to normoxic conditions. Moreover, the developed polymeric system was found non-toxic to MCF-7 cell line, thus suggesting its biocompatibility and suitability as drug delivery device.
a Key Laboratory of Polymer Ecomaterials , Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun , P.R. China.|b Department of Chemistry , Quaid-I-Azam University , Islamabad , Pakistan.
Zaheer
Z
Ahmad
a Key Laboratory of Polymer Ecomaterials , Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun , P.R. China.
Shixian
S
Lv
a Key Laboratory of Polymer Ecomaterials , Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun , P.R. China.
Zhaohui
Z
Tang
b Department of Chemistry , Quaid-I-Azam University , Islamabad , Pakistan.
Afzal
A
Shah
a Key Laboratory of Polymer Ecomaterials , Changchun Institute of Applied Chemistry, Chinese Academy of Sciences , Changchun , P.R. China.
Xuesi
X
Chen
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D000860:Hypoxia / Q000378:metabolism*; D061986:MCF-7 Cells; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D009593:Nitroimidazoles / Q000138:chemical synthesis / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D066244:Proton Magnetic Resonance Spectroscopy; D017550:Spectroscopy, Fourier Transform Infrared; D059016:Tumor Microenvironment / Q000502:physiology*
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008823:Micelles; D009593:Nitroimidazoles; C000610678:methoxy poly(ethylene glycol)-block-poly(glutamic acid)-graft-6-(2-nitroimidazole) hexyl amine; D011099:Polyglutamic Acid; D004317:Doxorubicin
,hypoxia responsive,; Drug delivery ; nitroimidazole, ; tumor microenvironment;  doxorubicin,