Co-Administered Polymeric Nano-Antidotes for Improved Photo-Triggered Response in Glioblastoma

Abstract

Polymer-based nanoparticles (NPs) are useful vehicles in treating glioblastoma because of their favorable characteristics such as small size and ability to cross the blood–brain barrier, as well as reduced immunogenicity and side effects. The use of a photosensitizer drug such as Verteporfin (BPD), in combination with a pan-vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI), Cediranib (CED), encapsulated in NPs will provide the medical field with new research on the possible ways to treat glioblastoma. Concomitant administration of BPD and CED NPs have the potential to induce dual photocytotoxic and cytostatic effects in U87 MG cells by (1) remotely triggering BPD through photodynamic therapy by irradiating laser at 690 nm and subsequent production of reactive oxygen species and (2) inhibiting cell proliferation by VEGFR interference and growth factor signaling mechanisms which may allow for longer progression free survival in patients and fewer systemic side effects. The specific aims of this research were to synthesize, characterize and assess cell viability and drug interactions for polyethylene-glycolated (PEGylated) polymeric based CED and BPD NPs which were less than 100 nm in size for enhanced permeation and retention effects. Synergistic effects were found using the co-administered therapies compared to the individual drugs. The major goal of this research was to investigate a new combination of photodynamic-chemotherapy drugs in nano-formulation for increased efficacy in glioblastoma treatment at reduced concentrations of therapeutics for enhanced drug delivery in vitro.

Improving Outcomes of Tyrosine Kinase Inhibitors in Hepatocellular Carcinoma: New Data and Ongoing Trials

“…The deliveries of apatinib and cediranib using polymeric nanoparticles were tested for osteosarcoma and glioblastoma, respectively. Both of the studies showed synergistic results compared to individual drugs (56,57). Moreover, micelle nanoparticles were also studied in a study.…”

The Role of Photoactivated and Non-Photoactivated Verteporfin on Tumor

“…In addition, laser-induced iNGR-VP-NA-DTX enhanced the inhibition of angiogenesis and induced severe apoptosis and necrosis in tumor tissues, but it had little effect on normal areas (DTX ranging from 1 ng/ml to 5 μg/ml; VP ranging from 10 ng/ml to 10 µg/ml, 0.6 J/cm 2 at 689 nm) ( Jiang et al, 2019 ). VP, VEGF tyrosine kinase inhibitor and cedrinaib were encapsulated in NPS by PDT via 690 nm laser irradiation to trigger BPD effect, as well as inhibit cell proliferation by VEGFR interference and growth factor signaling mechanism ( Kydd et al, 2018 ). The combination of three clinically related phosphatidylinositol 3-kinase (PI3K) pathway inhibitors (byl719, bkm120 and bez235) and VP PDT was evaluated.…”

Nanomedicine Revisited: Next Generation Therapies for Brain Cancer

“…for use as intratumoral and combination therapy against GBM. [ 175,176 ] Uniquely, Shah et al. studied the antitumor effects of PLGA‐based inhibitor of the Brachyury‐Yes‐associated protein axis in a BTIC model of GBM using GBM1A cells.…”