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Issue 8, 2017
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Tailored theranostic apolipoprotein E3 porphyrin-lipid nanoparticles target glioblastoma

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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

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Publication details

The article was received on 16 Feb 2017, accepted on 18 May 2017 and first published on 23 May 2017

Article type: Edge Article
DOI: 10.1039/C7SC00732A
Chem. Sci., 2017,8, 5371-5384
  • Open access: Creative Commons BY license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

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    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

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