Formulation and Characterization of Glioblastoma-Targeted Tailored ApoE Porphyrin Lipid Nanoparticles

Rajora, Maneesha 1, 2 ;  Ding, Lili 2 ;  Valic, Michael 1, 2 ;  Jiang, Wenlei 2 ;  Overchuk, Marta 1, 2 ;  Chen, Juan 2 ;  Zheng, Gang 1, 2, 3

1. Institute of Biomaterials and Biomedical Engineering, University of Toronto; 2. Princes Margaret Cancer Centre, University Health Network, Toronto; 3. Department of Medical Biophysics, University of Toronto

Motivation: Glioblastoma remains a highly fatal cancer of the brain, with a mere 5% five-year survival rate. An intact blood-brain barrier (BBB) and the diffuse infiltration of tumour cells into healthy brain parenchyma challenge the development of sensitive imaging platforms and curative treatment strategies for this aggressive brain cancer.


Purpose: Here, we present the development of porphyrin-lipid apolipoprotein E3 lipid nanoparticles (pyE-LN), which address these limitations while taking advantage of the theranostic properties of porphyrin supramolecular structures for cancer imaging and therapy. The inclusion of apoE3 in PyE-LN enables BBB permeation and the targeted the delivery of porphyrin through the high avidity binding of apoE3 to LDL receptors overexpressed by glioblastoma cells, where the unique photophysical properties of porphyrin can be exploited for targeted photodynamic therapy, and multimodal (fluorescence, PET, MRI) imaging.

Results and Conclusions: PyE-LNs compositions were tailored to generate discoidal and CO-loaded particles optimized for size, monodispersity, porphyrin loading and purity. Optical and physical characterization revealed the generation of monodisperse 30 nm particles with stable and efficient assembly of apoE3 and porphyrin, and strong fluorescence self-quenching. Cellular uptake of pyE-LNs activated the fluorescence of the shell-loaded monomeric porphyrin-lipid, allowing for characterization of pyE-LN targeting specificity in vitro and vivo. Particles demonstrated a 4-fold increased uptake in LDLR-overexpressing U87 glioblastoma cells compared to ldlA7s with minimal LDLR expression, and a tumour:healthy brain tissue specificity of 4:1.This tumour homing combined with the theranostic properties of porphyrin facilitated the specific imaging of orthotopic glioblastoma tumours via near-infrared fluorescence imaging. Thus, pyE-LN particles demonstrate a promising capacity to target glioblastoma tumours and improve drug and imaging agent delivery.