The most common primary brain tumour is glioblastoma multiforme (GBM). Despite latest cancer researches to improve the outcome of patients with GBM, this highly aggressive tumour remains one of the most difficult tumors to treat. Angiochem's Engineered Peptide Compounds (EPiC) provides a non-invasive and flexible platform for small and large molecules to treat brain diseases. Based on these properties, we have created a portfolio of new drug entities composed of siRNA, peptides and mAbs, The most advanced, ANG1005, is a new taxane derivative currently completing two Phase ½ clinical trials for the treatment of primary and secondary brain tumors. This EPiC drug is comprised of one Angiopep-2 peptide conjugated to three molecules of paclitaxel. Recently, Angiopep-2 has been shown to use the low-density lipoprotein related protein 1 (LRP1) has a gateway across the blood-brain barrier. Interestingly, LRP1 seems to be required in many tumours for the aggressive behaviour and is overexpressed in GBM. Here, we show an increase uptake of Angiopep-2 in implanted brain tumour using in vivo imaging when compared to the contralateral normal brain region. In these tumors, ANG1005 could be detected by LC/MS/MS analysis and immunohistochemistry. We next characterized Angiopep-2 and ANG1005 uptake in human U87 glioblastoma cell line. The transfection of U87 cells with siRNA LRP1 decreased the uptake of both Angiopep-2 and ANG1005 indicating that LRP1 is involved in their internalization in glioblastoma cells. Furthermore, we measured an increase in the uptake of both Angiopep-2 and ANG1005 in glioblastoma (U87) cells under three experimental conditions that mimic the aggressive cancer cell microenvironment: acidic pH, serum deprivation and hypoxia. Interestingly, under these conditions LRP1 expression was also increased. The increase of ANG1005 uptake and LRP1 expression indicates that the aggressive cancer microenvironment phenotype favors the entry of this anticancer drug into glioblastoma cells. Overall these results demonstrate that the EPiC drug ANG1005 can be an effective therapeutic strategy to target brain cancer cells and aggressive tumors such as GBM.