Oral administration of edelfosine encapsulated lipid nanoparticles causes regression of lung metastases in pre-clinical models of osteosarcoma

González-Fernández, Yolanda; Brown, Hannah; Patiño-García, Ana; Heymann, Dominique; Blanco-Prieto, María J.

doi:10.1016/j.canlet.2018.05.030

Cited by 26 publications

(18 citation statements)

References 26 publications

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“…Moreover, functional drug delivery system can also re-educate the tumor environment which involves tumor cells, immune cells, stomal cell, etc., to block the initiation of metastasis 125-128. Recently, edelfosine (ET), a potential anti-tumor agent with poor oral bioavailability and severe side effects, was encapsulated in lipid nanoparticles (ET-LNs) for osteosarcoma treatment by Gonzalez-Fernandez et al 126. Results of this study demonstrate that orally administered ET-LNs show significant growth inhibition effects in primary osteosarcoma cells.…”

Section: Strategies For Osteosarcoma-targeted Drug Deliverymentioning

confidence: 83%

Recent advances of drug delivery nanocarriers in osteosarcoma treatment

Wang¹,

Hu²,

Qing³

et al. 2020

J. Cancer

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Osteosarcoma is the most common primary malignant bone tumor mainly occurred in children and adolescence, and chemotherapy is limited for the side effects and development of drug resistance. Advances in nanotechnology and knowledge of cancer biology have led to significant improvements in developing tumor-targeted drug delivery nanocarriers, and some have even entered clinically application. Delivery of chemotherapeutic agents by functionalized smart nanocarriers could protect the drugs from rapid clearance, prolong the circulating time, and increase the drug concentration at tumor sites, thus enhancing the therapeutic efficacy and reducing side effects. Various drug delivery nanocarriers have been designed and tested for osteosarcoma treatment, but most of them are still at experimental stage, and more further studies are needed before clinical application. In this present review, we briefly describe the types of commonly used nanocarriers in osteosarcoma treatment, and discuss the strategies for osteosarcoma-targeted delivery and controlled release of drugs. The application of nanoparticles in the management of metastatic osteosarcoma is also briefly discussed. The purpose of this article is to present an overview of recent progress of nanoscale drug delivery platforms in osteosarcoma, and inspire new ideas to develop more effective therapeutic options.

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Section: Strategies For Osteosarcoma-targeted Drug Deliverymentioning

confidence: 83%

Recent advances of drug delivery nanocarriers in osteosarcoma treatment

Wang¹,

Hu²,

Qing³

et al. 2020

J. Cancer

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“…Perhaps, it would be of interest to perform these experiments in a tumor model that is more sensitive to the action of EF. For instance, orally administered EF loaded into solid lipid nanoparticles proved to be very efficacious in an HOS (ATCC ® CRL-1543™) orthotopic tumor model [ 35 ], although the EF IC 50 value in this cell line was 2.72 µM instead of 59 µM in the P1.15 cells.…”

Section: Discussionmentioning

confidence: 99%

Combinatorial Nanomedicine Made of Squalenoyl-Gemcitabine and Edelfosine for the Treatment of Osteosarcoma

Rodríguez-Nogales

Moreno

Zandueta

et al. 2020

Cancers

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Due to chemoresistance and a high propensity to form lung metastasis, survival rates in pediatric osteosarcoma (OS) are poor. With the aim to improve anticancer activity in pediatric OS, a multidrug nanomedicine was designed using the alkyl-lysophospholipid edelfosine (EF) co-assembled with squalenoyl–gemcitabine (SQ–Gem) to form nanoassemblies (NAs) of 50 nm. SQ–Gem/EF NAs modified the total Gem pool exposure in the blood stream in comparison with SQ–Gem NAs, which correlated with a better tolerability and a lower toxicity profile after multiple intravenous administrations in mice. For in vivo preclinical assessment in an orthotopic OS tumor model, P1.15 OS cells were intratibially injected in athymic nude mice. SQ–Gem/EF NAs considerably decreased the primary tumor growth kinetics and reduced the number of lung metastases. Our findings support the candidature of this anticancer nanomedicine as a potential pediatric OS therapy.

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“…Recently, González-Fernández et al have reported the combination of DOX and EDL and demonstrated synergistic effect in osteosarcoma cells; however, the study was limited to in vitro conditions. 25 In the present study, we have explored a detailed in vivo therapeutic efficacy in xenograft model and established the toxicity profile of free drugs and the nanoparticle-based combination.…”

Section: Introductionmentioning

confidence: 99%

<p>Doxorubicin and Edelfosine Combo-Loaded Lipid–Polymer Hybrid Nanoparticles for Synergistic Anticancer Effect Against Drug-Resistant Osteosarcoma</p>

Yang¹,

Wang²,

Liu³

et al. 2020

OTT

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Introduction: The failure of chemotherapy in osteosarcoma results in drug resistance and acute side effects in the body. Methods: In this study, we have prepared a novel folate receptor-targeted doxorubicin (DOX) and edelfosine (EDL)-loaded lipid-polymer hybrid nanoparticle (DE-FPLN) to enhance the anticancer efficacy in osteosarcoma. The nanoparticles were thoroughly characterized for in vitro biological assays followed by detailed antitumor efficacy analysis and toxicity analysis in a xenograft model. Results: The dual drug-loaded nanoparticles showed a nanosized morphology and physiological stability. The targeted nanoparticles showed enhanced cellular internalization and subcellular distribution in MG63 cancer cells compared to that of non-targeted nanoparticles. Among many ratios of DOX and EDL, 1:1 ratiometric combinations of drugs were observed to be highly synergistic in killing the cancer cells. MTT assay and caspase-3/7 activity assay clearly showed the superior anticancer efficacy of DE-FPLN formulations in inducing the cancer cell death. In vitro results indicate that the co-administration of two drugs in a folic acid-targeted nanoparticle could potentially induce the apoptosis and cell death. In vivo results displayed the potency of tumor cell killing and significant suppression of tumor growth without any detectable side effects. Conclusion: The lipid-polymer hybrid nanocarriers with multiple properties of high drug loading, sequential and ratiometric drug release, improved physiological stability, prolonged blood circulation, and tumor-specific targeting are promising for the delivery of multiple drugs in the treatment of osteosarcoma.

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Oral administration of edelfosine encapsulated lipid nanoparticles causes regression of lung metastases in pre-clinical models of osteosarcoma

Cited by 26 publications

References 26 publications

Recent advances of drug delivery nanocarriers in osteosarcoma treatment

Recent advances of drug delivery nanocarriers in osteosarcoma treatment

Combinatorial Nanomedicine Made of Squalenoyl-Gemcitabine and Edelfosine for the Treatment of Osteosarcoma

<p>Doxorubicin and Edelfosine Combo-Loaded Lipid–Polymer Hybrid Nanoparticles for Synergistic Anticancer Effect Against Drug-Resistant Osteosarcoma</p>

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