Safe lipid nanocapsule-based gel technology to target lymph nodes and combat mediastinal metastases from an orthotopic non-small-cell lung cancer model in SCID-CB17 mice

Wauthoz, Nathalie; Bastiat, Guillaume; Moysan, Elodie; Cieślak, Anna; Kondo, Kazuya; Zandecki, Marc; Moal, Valérie; Rousselet, Marie‐Christine; Hureaux, J.; Benoit, Jean‐Pierre

doi:10.1016/j.nano.2015.02.010

Cited by 24 publications

(10 citation statements)

References 35 publications

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“…1a). Thus, the physiochemical properties of these LNCs were similar for particles with and without DiD, as also reported by others [24]. The LNC particles were stable in PBS when stored at room temperature for more than 24 h (data not shown).…”

Section: Physiochemical Properties Of the Lncssupporting

confidence: 88%

Biological response and cytotoxicity induced by lipid nanocapsules

et al. 2020

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Background: Lipid nanocapsules (LNCs) are promising vehicles for drug delivery. However, since not much was known about cellular toxicity of these nanoparticles in themselves, we have here investigated the mechanisms involved in LNC-induced intoxication of the three breast cancer cell lines MCF-7, MDA-MD-231 and MDA-MB-468. The LNCs used were made of Labrafac ™ Lipophile WL1349, Lipoid ® S75 and Solutol ® HS15. Results: High resolution SIM microscopy showed that the DiD-labeled LNCs ended up in lysosomes close to the membrane. Empty LNCs, i.e. without encapsulated drug, induced not only increased lysosomal pH, but also acidification of the cytosol and a rapid inhibition of protein synthesis. The cytotoxicity of the LNCs were measured for up to 72 h of incubation using the MTT assay and ATP measurements in all three cell lines, and revealed that MDA-MB-468 was the most sensitive cell line and MCF-7 the least sensitive cell line to these LNCs. The LNCs induced generation of reactive free oxygen species and lipid peroxidation. Experiments with knock-down of kinases in the near-haploid cell line HAP1 indicated that the kinase HRI is essential for the observed phosphorylation of eIF2α. Nrf2 and ATF4 seem to play a protective role against the LNCs in MDA-MB-231 cells, as knock-down of these factors sensitizes the cells to the LNCs. This is in contrast to MCF-7 cells where the knock-down of these factors had a minor effect on the toxicity of the LNCs. Inhibitors of ferroptosis provided a large protection against LNC toxicity in MDA-MB-231 cells, but not in MCF-7 cells. Conclusions: High doses of LNCs showed a different degree of toxicity on the three cell lines studied, i.e. MCF-7, MDA-MD-231 and MDA-MB-468 and affected signaling factors and the cell fate differently in these cell lines.

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Section: Physiochemical Properties Of the Lncssupporting

confidence: 88%

Biological response and cytotoxicity induced by lipid nanocapsules

et al. 2020

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“…Another study looked at lipid-based nanocapsules in a hydrogel for lymphatic targeting. Wauthoz et al used a lauroyl derivative of gemcitabine and administered the formulation subcutaneously or intravenously to target the lymphatic system, decrease the toxicity associated with gemcitabine therapy, and fight against mediastinal metastases in a mouse model with orthotopic non-small cell lung cancer in immunodeficient mice [155]. The biodistribution study indicates that the nanocapsules were targeted to the lymph nodes, caused no significant myelosuppression compared to normal saline, and significantly prolonged survival compared to standard therapy and control.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Lymphatic changes in cancer and drug delivery to the lymphatics in solid tumors

Cote

Rao

Alany

et al. 2019

Advanced Drug Delivery Reviews

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Although many solid tumors use the lymphatic system to metastasize, there are few treatment options that directly target cancer present in the lymphatic system, and those that do are highly invasive, uncomfortable, and/or have limitations. This review gives a brief overview of lymphatic function and anatomy, discusses changes that befall the lymphatics in cancer and the mechanisms by which these changes occur, and presents limitations for drug delivery to the lymphatic system. We then go on to summarize relevant techniques and new research for targeting cancer populations in the lymphatics and enhancing drug delivery intralymphatically, including intralymphatic injections, isolated limb perfusion, passive nano drug delivery systems, and actively targeted nanomedicine.

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“…In addition to lymph-node targeting efficacy, SC administration was a promising alternative to conventional IV administration to avoid severe side effects due to too much systemic exposure to chemotherapeutics. Using gemcitabine-loaded LNCs, recent results have shown that SC administration reduced the myelosuppression that is observed after IV administration (22), at the same dose.…”

Section: Discussionmentioning

confidence: 99%

Passive and specific targeting of lymph nodes: the influence of the administration route

Pitorre¹,

Bastiat²,

Chatel³

et al. 2015

European Journal of Nanomedicine

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Abstract:Patients diagnosed with an advanced-stage cancer present a dismal prognosis due to the presence of metastases. From the primary tumor, the cancer cells are disseminated via lymphatic circulation; metastases develop initially in lymph nodes. Therefore, the targeting of lymph nodes needs to be improved in the design of future chemotherapy, and one way to ensure this targeting is by using the subcutaneous (SC) route. Using lipid nanocapsules (LNCs) (40 nm and fluorescently-labeled with DiD) as nanocarriers, a correlation between the SC injection site (behind the neck, the right and left flanks, and above the tail) for LNC administration and specific lymph node accumulation (left and right cervical, axillary and inguinal lymph nodes) was achieved for SpragueDawley rats. The pharmacokinetic and biodistribution profiles confirmed the absence of LNCs in systemic circulation after SC administration due to the optimal size of the LNCs. With appropriate SC administration, LNCs can accumulate in specific lymph nodes, whereas IV administration led to a weak accumulation of LNCs in all lymph nodes. Specific accumulation followed the lymph flow: bottom-up from the lower to upper limbs and top down from the head, with two lymph circulation partitions: right upper limb and the rest. Administration above the tail presented high inguinal and axillary lymph node accumulation whereas weak accumulation was observed after administration behind the neck. LNCs administered in the left flank only accumulated in the left inguinal and axillary lymph nodes, whereas left and right inguinal and axillary lymph nodes presented accumulation after administration in the right flank. Cervical lymph nodes, in the opposite direction of lymph flow, were never targeted after SC administration, whatever the injection site.

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Safe lipid nanocapsule-based gel technology to target lymph nodes and combat mediastinal metastases from an orthotopic non-small-cell lung cancer model in SCID-CB17 mice

Cited by 24 publications

References 35 publications

Biological response and cytotoxicity induced by lipid nanocapsules

Biological response and cytotoxicity induced by lipid nanocapsules

Lymphatic changes in cancer and drug delivery to the lymphatics in solid tumors

Passive and specific targeting of lymph nodes: the influence of the administration route

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