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Cytosolic delivery of LDL nanoparticle cargo using photochemical internalization

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Abstract

Following cellular delivery, most drugs must escape endosomes and lysosomes and reach the cytosol to be effective. This is particularly significant for nanoparticles, which can carry a large drug payload, but typically accumulate in endosomes and lysosomes. One attractive solution is to use light-triggered release, which can provide efficient endolysosomal membrane disruption and spatiotemporal control of cytosolic release. Here, we demonstrate the cytosolic release of cargo loaded into low density lipoprotein (LDL) nanoparticles using a photochemical internalization (PCI) approach. Three types of cargo-loaded LDL nanoparticles (CLLNPs) were generated by loading fluorescent dyes via (1) intercalation in the phospholipid monolayer exterior (surface loading), (2) conjugation to the amino acids of apoB-100 protein (protein loading) or (3) reconstitution into the hydrophobic core of LDL (core loading). Fluorescence imaging demonstrated the cellular uptake of CLLNPs was mediated by the LDL receptor and resulted in CLLNPs accumulation in endosomes. When cells were co-incubated with CLLNPs and AlPcS2a (a PCI agent), laser irradiation induced efficient cytosolic release of the surface-loaded and protein-labeled cargo, whereas the core-loaded hydrophobic dye could not readily be released. Thus, PCI is a useful cytosolic release method for CLLNPs, although the loading method must be considered.

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Authors and Affiliations

  1. Ontario Cancer Institute and Campbell Family Cancer Research Institute, TMDT 5-363, 101 College Street, Toronto, ON, M5G 1L7, Canada

    Honglin Jin, Jonathan F. Lovell, Juan Chen, Kenneth Ng, Weiguo Cao, Lili Ding, Zhihong Zhang & Gang Zheng

  2. Department of Medical Biophysics, University of Toronto, Toronto, Canada

    Honglin Jin & Gang Zheng

  3. Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada

    Jonathan F. Lovell, Kenneth Ng & Gang Zheng

  4. Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Wuhan, China

    Honglin Jin & Zhihong Zhang

Authors
  1. Honglin Jin
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  2. Jonathan F. Lovell
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  3. Juan Chen
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  4. Kenneth Ng
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  5. Weiguo Cao
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  6. Lili Ding
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  7. Zhihong Zhang
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  8. Gang Zheng
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Corresponding author

Correspondence to Gang Zheng.

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This article is published as part of a themed issue on immunological aspects and drug delivery technologies in PDT.

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Jin, H., Lovell, J.F., Chen, J. et al. Cytosolic delivery of LDL nanoparticle cargo using photochemical internalization. Photochem Photobiol Sci 10, 810–816 (2011). https://doi.org/10.1039/c0pp00350f

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  • DOI: https://doi.org/10.1039/c0pp00350f

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