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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 the   α  -hEGFR-ILs for the EGF receptor was evaluated  in vitro  using U87 mg and U251 mg cells and  in vivo  using an intracranial U87 mg xenograft model. The xenograft model was additionally analyzed with respect to permeability to endogenous albumin, tumor size, and vascularization. The  in vitro  studies revealed significantly higher binding of   α  -hEGFR-ILs when compared with liposomes conjugated with isotypic nonimmune immunoglobulin. The uptake and internalization of the   α  -hEGFR-ILs by U87 mg cells were further confirmed by 3D deconvolution analyses.  In vivo , the   α  -hEGFR-ILs accumulated to a higher extent inside the tumor when compared to nonimmune liposomes. The data show that   α  -hEGFR-ILs significantly enhance the uptake and accumulation of liposomes in this experimental model of GBM suggestive of improved specific nanoparticle-based delivery.

journal of drug delivery

Targeted Antiepidermal Growth Factor Receptor (Cetuximab) Immunoliposomes Enhance Cellular Uptake <i>In Vitro</i> and Exhibit Increased Accumulation in an Intracranial Model of Glioblastoma Multiforme

Targeted Antiepidermal Growth Factor Receptor (Cetuximab) Immunoliposomes Enhance Cellular Uptake In Vitro and Exhibit Increased Accumulation in an Intracranial Model of Glioblastoma Multiforme