Treatment of glioma by cisplatin-loaded nanogels conjugated with monoclonal antibodies against Cx43 and BSAT1

Abstract

(2015) Treatment of glioma by cisplatin-loaded nanogels conjugated with monoclonal antibodies against Cx43 and BSAT1, Drug Delivery, 22:3, 276-285, DOI: 10.3109/10717544.2013 AbstractTargeted 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.

Optical coefficients as tools for increasing the optical coherence tomography contrast for normal brain visualization and glioblastoma detection

“…Homogenized 101.8 glioblastoma (∼10 6 tumor cells) had been inoculated into the ventricle of the right hemisphere of the brain of each of the eight relevant rats using a standard procedure. 31 Glioblastoma 101.8 is a primary chemically induced brain tumor (grade IV), but after cultivation, it takes on morphological properties similar to human glioblastoma (high cellular density, cell polymorphism, presence of necrotic and hemorrhage areas, and infiltrative growth). CP OCT imaging was performed in four rats on days 7 to 9 after the glioma injection, when the tumor had matured but it did not have multiple necrosis; four rats were studied between 12 to 15 days, when extensive hemorrhages and necrosis appeared in the tumor.…”

“…The device has a 20,000 A-scans/s scanning rate and performs 2-D lateral scanning within an area of 2.4 × 2.4 mm 2 to obtain the 3-D distribution of backscattered light in the polarization with the same and reversed rotations of the electric-field vector. 31 Scanning was performed in contactless mode. An advantage of the CP OCT device used is its real-time image formation.…”

Nano carriers for drug transport across the blood–brain barrier

“…Two proteins, connexin 43 (Cx43) and brain-specific anion transporter 1 (BSAT1), which are promising targeted antigens for drug delivery to gliomas, have been respectively conjugated with the cisplatin-loaded nanogels prepared from aqueous solutions of poly(ethylene glycol) (PEG)-block-poly(methyl methylacrylate) (PMAA) and CaCl 2 using 1,2-ethylenediamine and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) as crosslinkers, for the treatment of intracranial gliomas [75]. 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 longer than that in control group, respectively, which suggested the effectiveness of the ligands in promoting BBB-penetrating efficiency of the nanogels.…”

Nanogels for delivery, imaging and therapy

“…The applications of nanogels in the field of cancer therapy are currently under rapid growth of interest with more focus on improving current therapies and diagnostic modalities . In a study on targeted nanogels, the therapeutic efficacy of cisplatin‐loaded nanogels was checked on glioma cells 101/8 . Nanogels were synthesized using poly(methacrylic acid) polymer cross‐linked with CaCl 2 .…”

“…Targeted nanogels significantly reduced the intrastriatal glioma in animals compared with the untreated control group. But no significance was observed for animals treated with targeted nanogels and free cisplatin . Claudin‐3 (CLDN3) upregulation in ovarian cancer was taken as a target by Liu et al, a short hairpin RNA was effectively loaded into biodegradable and biocompatible nanogel composed of heparin‐poly(ethylene imine) (HPEI).…”