Targeted Antiepidermal Growth Factor Receptor (Cetuximab) Immunoliposomes Enhance Cellular UptakeIn Vitroand Exhibit Increased Accumulation in an Intracranial Model of Glioblastoma Multiforme

摘要

Therapeutic advances do not circumvent the devastating fact that the survival rate in glioblastoma multiforme (GBM) is less than 5%. Nanoparticles consisting of liposome-based therapeutics are provided against a variety of cancer types including GBM, but available liposomal formulations are provided without targeting moieties, which increases the dosing demands to reach therapeutic concentrations with risks of side effects. We prepared PEGylated immunoliposomes (ILs) conjugated with anti-human epidermal growth factor receptor (EGFR) antibodies Cetuximab (α-hEGFR-ILs). The affinity of theα-hEGFR-ILs for the EGF receptor was evaluatedin vitrousing U87 mg and U251 mg cells andin vivousing an intracranial U87 mg xenograft model. The xenograft model was additionally analyzed with respect to permeability to endogenous albumin, tumor size, and vascularization. Thein vitrostudies revealed significantly higher binding ofα-hEGFR-ILs when compared with liposomes conjugated with isotypic nonimmune immunoglobulin. The uptake and internalization of theα-hEGFR-ILs by U87 mg cells were further confirmed by 3D deconvolution analyses.In vivo, theα-hEGFR-ILs accumulated to a higher extent inside the tumor when compared to nonimmune liposomes. The data show thatα-hEGFR-ILs significantly enhance the uptake and accumulation of liposomes in this experimental model of GBM suggestive of improved specific nanoparticle-based delivery.