Issue 8, 2017

Tailored theranostic apolipoprotein E3 porphyrin-lipid nanoparticles target glioblastoma


The development of curative glioblastoma treatments and tumour-specific contrast agents that can overcome the blood–brain barrier (BBB) and infiltrative tumour morphology remains a challenge. Apolipoprotein E3 (apoE3) is a high density lipoprotein apolipoprotein that chaperones the transcytosis of nanoparticles across the BBB, and displays high-affinity binding with the low density lipoprotein receptor (LDLR), a cell-surface receptor overexpressed by glioblastoma cells. This LDLR overexpression and apoE3 binding capacity was exploited for the development of glioblastoma-targeted porphyrin-lipid apoE3 lipid nanoparticles (pyE-LNs) with intrinsic theranostic properties. Size-controlled discoidal and cholesteryl oleate (CO)-loaded spherical pyE-LNs were synthesized through the systematic variation of particle composition, which dictated nanoparticle size and morphology. Composition optimization yielded 30 nm pyE-LNs with stable loading of apoE3 and porphyrin-lipid that simultaneously conferred the nanoparticles with glioblastoma targeting and activatable near-infrared fluorescence imaging functionalities. A 4-fold higher uptake of pyE-LNs by LDLR-expressing U87 glioblastomas cells relative to minimally expressing ldlA7 cells was observed in vitro. This uptake was a result of receptor-mediated endocytosis, which could be inhibited through LDL competition and acetylation of particle apoE3 moieties. ApoE3-dependent delivery of pyE-LN to glioblastomas was also demonstrated in orthotopic U87-GFP tumour-bearing animals. Quantification of CO-loaded pyE-LN biodistribution demonstrated successful selective uptake of porphyrin by malignant tissue, with a 4 : 1 tumour : healthy tissue particle specificity. This allowed for the detection of strong, tumour-localized porphyrin fluorescence, which was diminished when apoE3-devoid py-LN particles were administered. Furthermore, this selective uptake yielded cell-specific potent PDT sensitization in vitro, resulting in an 83% reduction in glioblastoma cell viability. These results highlight the promising capacity of pyE-LNs to target porphyrin delivery to glioblastoma tumours for theranostic applications.

Graphical abstract: Tailored theranostic apolipoprotein E3 porphyrin-lipid nanoparticles target glioblastoma

Associated articles

Supplementary files

Article information

Article type
Edge Article
16 Feb 2017
18 May 2017
First published
23 May 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2017,8, 5371-5384

Tailored theranostic apolipoprotein E3 porphyrin-lipid nanoparticles target glioblastoma

M. A. Rajora, L. Ding, M. Valic, W. Jiang, M. Overchuk, J. Chen and G. Zheng, Chem. Sci., 2017, 8, 5371 DOI: 10.1039/C7SC00732A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity