RETRACTED: Anti-Cancer Activities of Thyrointegrin αvβ3 Antagonist Mono- and Bis-Triazole Tetraiodothyroacetic Acid Conjugated via Polyethylene Glycols in Glioblastoma

Abstract

Integrin αvβ3 receptors are overexpressed in different tumors and their associated neovascularization and hence, represent a potential cancer target. We previously synthesized a high affinity thyrointegrin αvβ3, P4000-bi-TAT (tetrac derivative), with potent anticancer properties. However, the long polydisperse PEG conjugate showed large scaleup and analytical/bioanalytical issues. Hence, in the present study, we synthesized a mono versus bi-triazole tetrac with discrete monodisperse PEG, which provided improvement in scaleup and bioanalysis. In the present study, we compared binding affinity and anticancer activates with a smaller PEG size (P1600-bi-TAT, Compound 2) and the removal of one TAT molecule (P1600-m-TAT, Compound 3) versus P4000-bi-TAT, Compound 1. The results of the selectivity and affinity of TATs showed greater affinity to integrin αvβ3. The xenograft weights and tumor cell viabilities were decreased by >90% at all doses compared to the control (ON Treatment, *** p < 0.001) in cells treated with Compounds 1, 2, and 3 in U87-Luc-treated mice. The in vivo luminescent signals of U87-luc cells reflect the proliferation and distribution of tumor cells in the animals and the maximum intensity corresponding to the maximum tumor cells that the animals could tolerate. We found that the three thyrointegrin αvβ3 antagonists exhibited optimal therapeutic efficacy against U87 or primary glioblastoma cells. Biological studies showed that decreasing the PEG linker size (1600 vs. 4000) or having mono-TAT or bi-TAT had no significant impact on their αvβ3 binding affinity, anti-angiogenesis, or overall anti-cancer efficacy.

The Role of Graphene Oxide Nanocarriers in Treating Gliomas

“…Photodynamic therapy uses photo-biochemical processes to convert light energy into free radicals, which then play a role in inducing programmed cell death (136). U87-MG has been reported to cause an overexpression of integrin avb3 protein receptors (144). Pyropheophorbide-alpha (PPa) is a promising second-generation photosensitizer (145).…”

Correction: Godugu et al. Anti-Cancer Activities of Thyrointegrin αvβ3 Antagonist Mono- and Bis-Triazole Tetraiodothyroacetic Acid Conjugated via Polyethylene Glycols in Glioblastoma. Cancers 2021, 13, 2780

“…In the original publication [ 1 ], there was a mistake in the representative image for bFGF + Compound 3 . Specifically, in Figure 5A, there were unintentional mistakes in incorporating representative CAM images from other archived files.…”

Preclinical assessment of drug–drug interaction of fb‐PMT, a novel anti‐cancer thyrointegrin αvβ3 antagonist

“…6 The pharmacodynamic and pharmacokinetic properties of PEG-TAT conjugated molecules are attributed to the optimized chemical structure of this drug-polymer conjugate. [7][8][9][10] Drug-drug interactions (DDIs) are problematic when a drug candidate enters into clinical applications because they may affect pharmacokinetic and pharmacodynamic properties of other pharmaceuticals administered at the same time. 11 Preclinical assessment of DDIs is, therefore, important to minimize potential adverse effects of drug candidates when they are used in the clinical setting.…”