Treatment of glioma by cisplatin-loaded nanogels conjugated with monoclonal antibodies against Cx43 and BSAT1.
Targeted drug delivery for brain tumor treatment is one of the important objectives in nanomedicine. Human glioblastoma is the most frequent and aggressive type of brain tumors. The preferential expression of membrane protein connexin 43 (Cx43) and brain-specific anion transporter (BSAT1) in the tumor and peritumoral area is a key component for targeted drug delivery. The purpose of this study was to design cisplatin-loaded nanogels conjugated with monoclonal antibodies to Cx43 and BSAT1 for treatment of intracranial gliomas 101/8. MRI volumetric analysis of tumor-bearing rats indicated significantly reduced tumor volume with cisplatin-loaded targeted-nanogel treatment compared to other formulations. The median survival of rats treated with targeted nanogels conjugated with specific mAbs against extracellular loops of Cx43 and BSAT1 were 27 and 26.6 days higher than that in control group, respectively. For the first time we demonstrated the efficiency of mAb-targeted cisplatin-loaded nanogels in the experimental model of glioma 101/8. This approach could facilitate the development of new drug delivery systems for the treatment of gliomas.
Department of Medicinal Nanobiotechnology, Pirogov Russian State Medical University , Moscow , Russia .
Vladimir P
VP
Baklaushev
Natalia N
NN
Nukolova
Alexander S
AS
Khalansky
Olga I
OI
Gurina
Gaukhar M
GM
Yusubalieva
Nadejhda Ph
NP
Grinenko
Ilya L
IL
Gubskiy
Pavel A
PA
Melnikov
Karina Sh
KSh
Kardashova
Alexander V
AV
Kabanov
Vladimir P
VP
Chekhonin
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018031:Connexin 43 / Q000037:antagonists & inhibitors*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D005782:Gels / Q000737:chemistry; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049329:Nanostructures / Q000737:chemistry; D009368:Neoplasm Transplantation; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors*; D017208:Rats, Wistar; D016019:Survival Analysis
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018031:Connexin 43; D004337:Drug Carriers; D005782:Gels; C580592:Gja1 protein, rat; D027701:Organic Cation Transport Proteins; C451262:Slco1c1 protein, rat; D002945:Cisplatin
Connexin-43; glioblasoma multiforme; monoclonal antibody; nanogels; targeted delivery