Mitochondrial targeting by use of lipid nanocapsules loaded with SV30, an analogue of the small-molecule Bcl-2 inhibitor HA14-1

Weyland, M; Manero, Florence; Paillard, Archibald; Grée, Danielle; Viault, Guillaume; Jarnet, D.; Menei, Philippe; Juin, Philippe; Chourpa, Igor; Benoit, Jean‐Pierre; Grée, René; Garcion, Emmanuel

doi:10.1016/j.jconrel.2010.11.032

Cited by 30 publications

(11 citation statements)

References 65 publications

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“…Mitochondria also happen to be the key regulators of apoptosis [3, 12–14] by triggering the complex cell-death processes by a variety of mechanisms including translocation of the pro-apoptotic proteins such as cytochrome- C , apoptosis-inducing factor from the mitochondrial inter-membrane space to the cytosol, which then activate the death-signal proteins such as caspases [15, 16]. Since the mitochondria play a pivotal role in cell-death, a mitochondria-targeted treatment strategy could be promising for cancer therapy [17]. Thus, there is increasing evidence that the cytotoxic effect of the potent chemotherapeutic drug PTX is mediated through mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Liposomes loaded with paclitaxel and modified with novel triphenylphosphonium-PEG-PE conjugate possess low toxicity, target mitochondria and demonstrate enhanced antitumor effects in vitro and in vivo

Biswas

Dodwadkar

Deshpande

et al. 2012

Journal of Controlled Release

243

160

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Previously, stearyl triphenylphosphonium (STPP)-modified liposomes (STPP-L) were reported to target mitochondria. To overcome a non-specific cytotoxicity of STPP-L, we synthesized a novel polyethylene glycol- phosphatidylethanolamine (PEG-PE) conjugate with the TPP group attached to the distal end of the PEG block (TPP-PEG-PE). This conjugate was incorporated into the liposomal lipid bilayer, and the modified liposomes were studied for their toxicity, mitochondrial targeting, and efficacy in delivering paclitaxel (PTX) to cancer cells in vitro and in vivo. These TPP-PEG-PE-modified liposomes (TPP-PEG-L), surface grafted with as high as 8 mole % of the conjugate, were less cytotoxic compared to STPP-L or PEGylated STPP-L. At the same time, TPP-PEG-L demonstrated efficient mitochondrial targeting in cancer cells as shown by confocal microscopy in co-localization experiments with stained mitochondria. PTX-loaded TPP-PEG-L demonstrated enhanced PTX-induced cytotoxicity and anti-tumor efficacy in cell culture and mouse experiments compared to PTX-loaded unmodified plain liposomes (PL). Thus, TPP-PEG-PE can serve as a targeting ligand to prepare non-toxic liposomes as mitochondria-targeted drug delivery systems (DDS).

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Section: Introductionmentioning

confidence: 99%

Liposomes loaded with paclitaxel and modified with novel triphenylphosphonium-PEG-PE conjugate possess low toxicity, target mitochondria and demonstrate enhanced antitumor effects in vitro and in vivo

Biswas

Dodwadkar

Deshpande

et al. 2012

Journal of Controlled Release

243

160

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“…Novel LNC formulations towards the development of new mitochondria-targeted medicines have been proposed to improve the administration and biological activity of an analogue of the pro-apoptotic molecule HA14-1 (38). HA14-1 was designed to inhibit Bcl-2/Bax interactions and thus stimulate apoptosis (39).…”

Section: Lipid Nanocapsulesmentioning

confidence: 99%

“…HA14-1 was designed to inhibit Bcl-2/Bax interactions and thus stimulate apoptosis (39). Subsequently, due to the instability of the molecule, a more stable analogue of HA14-1, called SV30, was prepared (40) and evaluated against glioma cells (38). SV30 was incorporated into LNCs at a high encapsulation rate, and its stability was maintained during the formulation process.…”

Section: Lipid Nanocapsulesmentioning

confidence: 99%

“…Of note, unlike the other studies mentioned in this section, LNC size was affected by the loading of the lipophilic drug, resulting in a 20% increase compared to unloaded LNCs. Thus, LNC size and, more discretely, ZP modifications post-encapsulation combined with the relatively fast release of SV30 suggested that the drug might also be present on the external shell of the LNCs (38). Empty LNCs had no effect on glioma cells, while the SV30-LNCs triggered a 2-fold increase in cancer cell death compared to free SV30.…”

Section: Lipid Nanocapsulesmentioning

confidence: 99%

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Developments in the use of nanocapsules in oncology

Yurgel

Collares

Seixas

2013

Braz J Med Biol Res

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The application of nanotechnology to medicine can provide important benefits, especially in oncology, a fact that has resulted in the emergence of a new field called Nanooncology. Nanoparticles can be engineered to incorporate a wide variety of chemotherapeutic or diagnostic agents. A nanocapsule is a vesicular system that exhibits a typical core-shell structure in which active molecules are confined to a reservoir or within a cavity that is surrounded by a polymer membrane or coating. Delivery systems based on nanocapsules are usually transported to a targeted tumor site and then release their contents upon change in environmental conditions. An effective delivery of the therapeutic agent to the tumor site and to the infiltrating tumor cells is difficult to achieve in many cancer treatments. Therefore, new devices are being developed to facilitate intratumoral distribution, to protect the active agent from premature degradation and to allow its sustained and controlled release. This review focuses on recent studies on the use of nanocapsules for cancer therapy and diagnosis.

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“…Their size can be tuned within the range of 20-100 nm [9]. LNC have been used for the delivery of cancer therapeutics [10][11][12][13] and other drug molecules [14], macromolecules such as siRNA and DNA [15], and radiotherapeutics [16][17][18]. In the context of radiotherapy, 188 Re-LNC have been tested for locoregional treatment of glioma in rats by stereotactic administration [18].…”

Section: Introductionmentioning

confidence: 99%

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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Mitochondrial targeting by use of lipid nanocapsules loaded with SV30, an analogue of the small-molecule Bcl-2 inhibitor HA14-1

Cited by 30 publications

References 65 publications

Liposomes loaded with paclitaxel and modified with novel triphenylphosphonium-PEG-PE conjugate possess low toxicity, target mitochondria and demonstrate enhanced antitumor effects in vitro and in vivo

Liposomes loaded with paclitaxel and modified with novel triphenylphosphonium-PEG-PE conjugate possess low toxicity, target mitochondria and demonstrate enhanced antitumor effects in vitro and in vivo

Developments in the use of nanocapsules in oncology

Tumour targeting of lipid nanocapsules grafted with cRGD peptides

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