Dual-Targeting Temozolomide Loaded in Folate-Conjugated Magnetic Triblock Copolymer Nanoparticles to Improve the Therapeutic Efficiency of Rat Brain Gliomas

Abstract

In order to conduct an effective chemotherapy session as a treatment modality for glioblastoma tumors, a nanocarrier platform is required for the drug to cross the blood brain barrier (BBB) successfully and properly target glioma cells. Dual-targeting Temozolomide (TMZ) loaded triblock polymer coated magnetic nanoparticles (MNPs) were synthesized with a SPION core and by conjugating the surface with folic acid (FA), which were shown to effectively pass the BBB and target tumor cells. Two principal methods, dynamic light scattering (DLS) and transmission electron microscopy (TEM) were employed for characterization of the synthesized nanoparticles. TMZ-loaded MNP-FA nanoparticles presented with a size of 58.61 nm, a zeta potential of −29.85 ± 0.47 mV, and a drug loading content of 6.85 ± 0.46%. Data gathered from inductively coupled plasma optical emission spectrometry (ICP-OES) and Prussian blue staining indicated effective dual-targeting, which subsequently led to an appreciably enhanced penetration through the BBB and accumulation of MNPs-FA in rat glioma cells. The anticancer effect of the dual-targeting MNPs-FA was also indicated by the increased survival time (>100%, p < 0.001) and decreased tumor volume (p < 0.001). In conclusion, the dual-targeting TMZ-loaded MNPs-FA are able to improve therapeutic efficiency toward brain gliomas in rats.

The Interaction of Temozolomide with Blood Components Suggests the Potential Use of Human Serum Albumin as a Biomimetic Carrier for the Drug

“…This study not only contributes to the further understanding of the bioavailability of TMZ, but can also be used to design more efficient formulations, which increase the stability and therapeutic index of the drug, a task that has been pursued by a large number of laboratories for years [1,12,[81][82][83][84][85][86]. In this regard, HSA-based nanocarriers seem to be suitable candidates for designing biomimetic delivery systems that selectively transport TMZ to GBM cells.…”

Excretable, ultrasmall hexagonal NaGdF4:Yb50% nanoparticles for bimodal imaging and radiosensitization

“…(Arvold and Reardon 2014) A major factor that contributes to poor prognosis in GBM patients is the limited response to treatment caused by the inability of most chemotherapeutic agents to cross the blood-brain barrier (BBB). We demonstrate here that the ultrasmall size of the nanoparticles conjugated with folic acid can take advantage of the folate receptor expressed at the BBB (Afzalipour et al 2019;Wu and Pardridge 1999) to facilitate the transport of the nanoparticles across BBB. Advanced MRI and CT imaging techniques such as dynamic contrast-enhanced (DCE) imaging, which monitors the temporal changes in contrast enhancement in blood vessels and tissues to provide a time-concentration curve, are promising non-invasive methods with moderate-to-high accuracy in stratifying tumors and discriminating recurrent lesions and treatment-related changes.…”

Excretable, ultrasmall hexagonal NaGdF4:Yb50% Nanoparticles for bimodal imaging and radiosensitization

“…[36] A major factor that contributes to poor prognosis in GBM patients is the limited response to treatment caused by the inability of most chemotherapeutic agents to cross the blood-brain barrier (BBB). We demonstrate here that the ultrasmall size of the nanoparticles conjugated with folic acid can take advantage of the folate receptor expressed at the BBB [37,38] to facilitate the transport of the nanoparticles across BBB. Advanced MRI and CT imaging techniques such as dynamic contrast-enhanced (DCE) imaging, which monitors the temporal changes in contrast enhancement in blood vessels and tissues to provide a time-concentration curve, are promising non-invasive methods with moderate to high accuracy in stratifying tumors and discriminating recurrent lesions and treatmentrelated changes.…”