The importance of endo-lysosomal escape with lipid nanocapsules for drug subcellular bioavailability

Paillard, Archibald; Hindré, François; Vignes-Colombeix, Caroline; Benoit, Jean‐Pierre; Garcion, Emmanuel

doi:10.1016/j.biomaterials.2010.06.024

Cited by 126 publications

(83 citation statements)

References 66 publications

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“…This observation is reminiscent of the previously described active internalization of LNC at 37 °C [48]. Instead, no such differences were observed when cells were treated with LNC- Comparable results were obtained when cRGD-lipid nanoparticles that are structurally analogical to LNC were used to target HEK293(β3) cells [34]: FACS analysis revealed equal fluorescence intensity after incubation at 4 °C and 37 °C.…”

Section: In Vivo Biodistributionsupporting

confidence: 72%

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Tumour targeting of lipid nanocapsules grafted with cRGD peptides

Hirsjärvi

Belloche

Hindré

et al. 2014

European Journal of Pharmaceutics and Biopharmaceutics

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Combining targeting to therapy remains a major challenge in cancer treatment. To address this subject, the surface of lipid nanocapsules (LNC) were modified by grafting cRGD peptides, which are known to be recognised by α v β 3 integrins expressed by tumour endothelium and cancer cells. Applicability of this LNC-cRGD in tumour targeting was first assessed in vitro by the use of U87MG glioma cells. Biodistribution and tumour accumulation of radiolabelled LNC-cRGD in vivo were then evaluated in mice bearing the same subcutaneous xenograft. Flow cytometry and confocal microscopy results revealed that the cRGD grafting improved binding and internalization compared to negative control LNCcRAD and blank LNC. The peptide-grafted LNC remained in the blood circulation up to 3 hours with reduced capture by the RES organs. Tumour accumulation of LNC-cRGD with respect to LNC-cRAD was significantly higher at 1-3 hours. These results show that cRGD grafted to LNC has created a promising tumour-targetable nanocarrier that could be used in cancer treatment.

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Section: In Vivo Biodistributionsupporting

confidence: 72%

“…Cell detachment observed at high concentrations of LNC, LNC-cRGD and LNC-cRAD could mainly result from non-specific interactions between the LNC surfactant and the cell membranes as previously established [48].…”

Section: In Vivo Biodistributionsupporting

confidence: 65%

Tumour targeting of lipid nanocapsules grafted with cRGD peptides

Hirsjärvi

Belloche

Hindré

et al. 2014

European Journal of Pharmaceutics and Biopharmaceutics

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“…Drug loading ranged from 6% to 7% w/w for decitabine-loaded nanogels 7 and was 8.54%±2.65% in lipid-based nanocarriers developed by Neupane et al 10 The size obtained in our formulation was less than that of previously developed formulations, ranging from 80 to 200 nm. 9,10,30,31 Paillard et al have demonstrated that the number of LNCs internalized into cells is inversely proportional to their size, 32 suggesting that the size obtained for the THP-T80-LNC formulation could favor internalization. Moreover, no organic solvent was used and no decitabine-chemical modification was made in the THP-T80-LNC formulations, in contrast to previous formulations developed to encapsulate decitabine.…”

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confidence: 99%

“…The improved cytotoxic effect may also be explained by the ability of LNCs to be internalized by cells via endocytosis. 32 LNCs could thus facilitate the translocation of decitabine across the cellular membrane, which is generally carried out by nucleoside transporters, such as hENT1. 26,37,38 Thus, both the pathways could be used: free-drug through hENT 1 transport and decitabine-loaded THP-T80-LNCs through the endocytosis pathway.…”

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confidence: 99%

Development and in vitro evaluations of new decitabine nanocarriers for the treatment of acute myeloid leukemia

Briot

Roger

Lautram

et al. 2017

IJN

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“…23 LNCs accumulate rapidly within cells without the need for transfection agents, and they can bypass the endolysosomal compartment and overcome the multidrug-resistance mechanism. 24,25 In previous studies, we encapsulated an organometallic complex analog of 4-hydroxytamoxifen called ferrociphenol (Fc-diOH) in LNCs. Fc-diOH was developed by adding a ferrocene moiety to the tamoxifen skeleton.…”

mentioning

confidence: 99%

Targeting and treatment of glioblastomas with human mesenchymal stem cells carrying ferrociphenol lipid nanocapsules

Clavreul¹,

Montagu²,

Lainé³

et al. 2015

IJN

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Recently developed drug delivery nanosystems, such as lipid nanocapsules (LNCs), hold great promise for the treatment of glioblastomas (GBs). In this study, we used a subpopulation of human mesenchymal stem cells, "marrow-isolated adult multilineage inducible" (MIAMI) cells, which have endogenous tumor-homing activity, to deliver LNCs containing an organometallic complex (ferrociphenol or Fc-diOH), in the orthotopic U87MG GB model. We determined the optimal dose of Fc-diOH-LNCs that can be carried by MIAMI cells and compared the efficacy of Fc-diOH-LNC-loaded MIAMI cells with that of the free-standing Fc-diOH-LNC system. We showed that MIAMI cells entrapped an optimal dose of about 20 pg Fc-diOH per cell, with no effect on cell viability or migration capacity. The survival of U87MG-bearing mice was longer after the intratumoral injection of Fc-diOH-LNC-loaded MIAMI cells than after the injection of Fc-diOH-LNCs alone. The greater effect of the Fc-diOH-LNC-loaded MIAMI cells may be accounted for by their peritumoral distribution and a longer residence time of the drug within the tumor. These results confirm the potential of combinations of stem cell therapy and nanotechnology to improve the local tissue distribution of anticancer drugs in GB.

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The importance of endo-lysosomal escape with lipid nanocapsules for drug subcellular bioavailability

Cited by 126 publications

References 66 publications

Tumour targeting of lipid nanocapsules grafted with cRGD peptides

Tumour targeting of lipid nanocapsules grafted with cRGD peptides

Development and in vitro evaluations of new decitabine nanocarriers for the treatment of acute myeloid leukemia

Targeting and treatment of glioblastomas with human mesenchymal stem cells carrying ferrociphenol lipid nanocapsules

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