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.
Highlights
Glioblastoma multiforme (GBM) accounts for approximately 40% of all high-grade, type IV, intracranial tumors [1]
The variety of drug interactions found in this study provided a basis for understanding how CED and BPD cell viability effects are concentration-dependent, whereby additive, synergistic and antagonistic behaviors were observed according to viability and Coefficient of Drug Interaction (CDI) results
Triggering agents that cause cytotoxicity in and around the tumor may help reduce the morbidities typically associated with chemotherapies [75]
Summary
Glioblastoma multiforme (GBM) accounts for approximately 40% of all high-grade, type IV, intracranial tumors [1]. GBM, a subtype of glioma, or glial cell origin tumor, affects the brain or spinal cord and is characterized by aggressive metastatic potential with poor survival outcomes of 14 months with traditional treatments [1]. Histological analysis of GBM tumors show finger-like astrocytes which extend into the deeper regions of the brain tissue, making surgical and adjuvant therapies futile [3]. Less invasive and tumor-targeted options are mandated, as unspecified cytotoxicity and deleterious side effects waiver a grim cost versus benefit in long term survival and quality of life for GBM patients [2,8,9]
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