Formulation optimization of an ephrin A2 targeted immunoliposome encapsulating reversibly modified taxane prodrugs

Huang, Zhongdong; Tipparaju, Suresh K.; Kirpotin, Dmitri B.; Pien, Christine; Kornaga, Tad; Noble, Charles O.; Koshkaryev, Alexander; Tran, Jimmy; Kamoun, Walid S.; Drummond, Daryl C.

doi:10.1016/j.jconrel.2019.08.006

Cited by 30 publications

(20 citation statements)

References 41 publications

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“…The stability and in vitro drug release studies illustrated that the encapsulated MTX could not only achieve long-term circulation of the drug in the body but also realize specific drug release in the acidic tumor environment. These two properties are essential for the antitumor nano-formulations, as they can reduce toxicity and increase efficacy [ 50 , 51 ].…”

Section: Resultsmentioning

confidence: 99%

Nucleoside transporter-guided cytarabine-conjugated liposomes for intracellular methotrexate delivery and cooperative choriocarcinoma therapy

Fei

Zhao

et al. 2021

J Nanobiotechnol

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Gestational trophoblastic tumors seriously endanger child productive needs and the health of women in childbearing age. Nanodrug-based therapy mediated by transporters provides a novel strategy for the treatment of trophoblastic tumors. Focusing on the overexpression of human equilibrative nucleoside transporter 1 (ENT1) on the membrane of choriocarcinoma cells (JEG-3), cytarabine (Cy, a substrate of ENT1)-grafted liposomes (Cy-Lipo) were introduced for the targeted delivery of methotrexate (Cy-Lipo@MTX) for choriocarcinoma therapy in this study. ENT1 has a high affinity for Cy-Lipo and can mediate the endocytosis of the designed nanovehicles into JEG-3 cells. The ENT1 protein maintains its transportation function through circulation and regeneration during endocytosis. Therefore, Cy-Lipo-based formulations showed high tumor accumulation and retention in biodistribution studies. More importantly, the designed DSPE-PEG2k-Cy conjugation exhibited a synergistic therapeutic effect on choriocarcinoma. Finally, Cy-Lipo@MTX exerted an extremely powerful anti-choriocarcinoma effect with fewer side effects. This study suggests that the overexpressed ENT1 on choriocarcinoma cells holds great potential as a high-efficiency target for the rational design of active targeting nanotherapeutics. Graphic abstract

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Section: Resultsmentioning

confidence: 99%

Nucleoside transporter-guided cytarabine-conjugated liposomes for intracellular methotrexate delivery and cooperative choriocarcinoma therapy

Fei

Zhao

et al. 2021

J Nanobiotechnol

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“…For example, membrane-bound hepatocellular receptor tyrosine kinase class A2 (EphA2) is overexpressed in various types of cancers and related with several signaling pathways of invasion and metastasis [154]. Merrimack Pharmaceuticals established a taxane-liposome coated with anti-EphA2 scFvs, which showed improved efficiency and specificity [155].…”

Section: Direct Target Transmembrane Signaling On Tumor Cellsmentioning

confidence: 99%

Smart Lipid-Based Nanosystems for Therapeutic Immune Induction against Cancers: Perspectives and Outlooks

2021

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Cancer immunotherapy, a promising and widely applied mode of oncotherapy, makes use of immune stimulants and modulators to overcome the immune dysregulation present in cancer, and leverage the host’s immune capacity to eliminate tumors. Although some success has been seen in this field, toxicity and weak immune induction remain challenges. Liposomal nanosystems, previously used as targeting agents, are increasingly functioning as immunotherapeutic vehicles, with potential for delivery of contents, immune induction, and synergistic drug packaging. These systems are tailorable, multifunctional, and smart. Liposomes may deliver various immune reagents including cytokines, specific T-cell receptors, antibody fragments, and immune checkpoint inhibitors, and also present a promising platform upon which personalized medicine approaches can be built, especially with preclinical and clinical potentials of liposomes often being frustrated by inter- and intrapatient variation. In this review, we show the potential of liposomes in cancer immunotherapy, as well as the methods for synthesis and in vivo progression thereof. Both preclinical and clinical studies are included to comprehensively illuminate prospects and challenges for future research and application.

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“…The stability and in vitro drug release studies illustrated that the liposome-encapsulated MTX could not only achieve the long-term circulation of the drug in the body but also realized the speci c drug release in the acidic tumor environment. These two properties are essential for anti-tumor nano-formulations, as they can reduce the toxicity and increase the e cacy [48,49].…”

Section: In Vitro Drug Releasementioning

confidence: 99%

Nucleoside Transporter-guided Cytarabine Conjugated Liposomes for Intracellular Methotrexate Delivery and Cooperative Choriocarcinoma Therapy

Fei

Zhao

et al. 2021

Preprint

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The gestational trophoblastic tumor seriously endangers child productive needs and the health of women in childbearing age. Nanodrug-based therapy mediated by transporters provides novel strategy for the treatment of trophoblastic tumors. Focus on the overexpressed human equilibrative nucleoside transporter 1 (ENT1) on the membrane of choriocarcinoma cells (JEG-3), the cytarabine (Cy, a substrate of ENT1) grafted liposome (Cy-Lipo) was introduced for targeted delivery of methotrexate (Cy-Lipo@MTX) for choriocarcinoma therapy in this study. The ENT1 has high affinity for Cy-Lipo and can mediate the endocytosis of the designed nanovehicles into JEG-3 cells. The ENT1 protein maintains its transporting function through circulation and regeneration during endocytosis. Therefore, Cy-Lipo-based formulations achieved high tumor accumulation and retention in pharmacokinetic and distribution studies. More importantly, the designed Cy-lipid conjugation exhibited a synergistic therapeutic effect on choriocarcinoma. Finally, Cy-Lipo@MTX exerts an extremely powerful anti-choriocarcinoma effect with fewer side effects. This study suggests that the overexpressed ENT1 on choriocarcinoma cells holds a great potential to be a high-efficiency target for the rational design of active targeting nanotherapeutics.

show abstract

Formulation optimization of an ephrin A2 targeted immunoliposome encapsulating reversibly modified taxane prodrugs

Cited by 30 publications

References 41 publications

Nucleoside transporter-guided cytarabine-conjugated liposomes for intracellular methotrexate delivery and cooperative choriocarcinoma therapy

Nucleoside transporter-guided cytarabine-conjugated liposomes for intracellular methotrexate delivery and cooperative choriocarcinoma therapy

Smart Lipid-Based Nanosystems for Therapeutic Immune Induction against Cancers: Perspectives and Outlooks

Nucleoside Transporter-guided Cytarabine Conjugated Liposomes for Intracellular Methotrexate Delivery and Cooperative Choriocarcinoma Therapy

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