Overcoming drug-resistant lung cancer by paclitaxel loaded dual-functional liposomes with mitochondria targeting and pH-response

Jiang, Lei; Li, Li; He, Xin; Yi, Qiangying; He, Bin; Cao, Jun; Pan, Weisan; Gu, Zhongwei

doi:10.1016/j.biomaterials.2015.02.004

Cited by 267 publications

(173 citation statements)

References 60 publications

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“…Since then, different death-inducing peptides were targeted for tumor cells via various specific ligands, such as CNGRC, RGD, anti-neuropilin-1 (NRP-1), or E-selectin binding peptides, as well as with small ligands, such as folic acid. [48][49][50][51] The amphipathic toxic peptides are characterized by their positive charges, which enable them to bind to negatively charged cell membranes and cause their disruption, eventually leading to cell death. Their mode of action can vary.…”

Section: Discussionmentioning

confidence: 99%

Systemic Delivery of Tumor-Targeted Bax-Derived Membrane-Active Peptides for the Treatment of Melanoma Tumors in a Humanized SCID Mouse Model

et al. 2017

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Melanoma is a highly metastatic and deadly form of cancer. Invasive melanoma cells overexpress integrin a v b 3 , which is a well-known target for Arg-Gly-Asp-based (RGD) peptides. We developed a sophisticated method to synthetize milligram amounts of a targeted vector that allows the RGD-mediated targeting, internalization, and release of a mitochondria-disruptive peptide derived from the pro-apoptotic Bax protein. We found that 2.5 mM Bax[109-127] was sufficient to destabilize the mitochondria in ten different tumor cell lines, even in the presence of the anti-apoptotic Bcl2 protein, which is often involved in tumor resistance. This pore-forming peptide displayed antitumor activity when it was covalently linked by a disulfide bridge to the tetrameric RAFT-c[RGD] 4 -platform and after intravenous injection in a human melanoma tumor model established in humanized immuno-competent mice. In addition to its direct toxic effect, treatment with this combination induced the release of the immuno-stimulating factor monocyte chimoattractant protein 1 (MCP1) in the blood and a decrease in the level of the pro-angiogenic factor FGF2. Our novel multifunctional, apoptosis-inducing agent could be further customized and assayed for potential use in tumortargeted therapy.

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Section: Discussionmentioning

confidence: 99%

Systemic Delivery of Tumor-Targeted Bax-Derived Membrane-Active Peptides for the Treatment of Melanoma Tumors in a Humanized SCID Mouse Model

et al. 2017

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“…Caspase-3 activity appears to regulate the speed of this response. The study of caspase-3 -/-and caspase-9 -/-mice suggested the caspase pathway used for disassembly is cell type specific (20)(21)(22). Our findings suggest that control of HO-1 expression contributes to this process.…”

Section: Discussionmentioning

confidence: 60%

Evaluation of HO-1 expression, cellular ROS production, cellular proliferation and cellular apoptosis in human esophageal squamous cell carcinoma tumors and cell lines

Ren

Yang

et al. 2016

Oncology Reports

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Abstract.Patients with esophageal squamous cell carcinoma (ESCC) have a poor prognosis. However, the related mechanisms are unclear, thus we investigated the expression of HO-1 in ESCC tissue and explored possible mechanisms of tumor progression. Expression of HO-1 was examined by immunohistochemistry in 143 ESCC tumors. The correlation of HO-1 with clinicopathological characteristics was also examined. Two human ESCC cell lines, TE-13 and Eca109 were studied. Silencing of cell line HO-1 by specific small interfering RNA (siRNA) was evaluated using real-time quantitative PCR. Cell line viability, apoptosis and intracellular levels of reactive oxygen species (ROS) after transfection were determined using MTT and flow cytometry, respectively. HO-1, Bax, Bcl-2 and A-caspase-3/-9 expression was evaluated using western blot analyses. We found that HO-1 was expressed in 58 of 143 ESCC tumors, mainly in the cytoplasm. There was a significant association between HO-1 expression and tumor grade (P<0.001). Knockdown of HO-1 expression in cell lines was associated with significantly decreased cellular proliferation (P<0.05) and a higher rate of apoptosis (P<0.001) 48 h after treatment. Treatment of the cell lines with the ROS inhibitor N-acetylcysteine abrogated this effect. Knockdown of HO-1 was associated with increased A-caspase-3 and -9 expression, but no change in Bax or Bcl-2 expression or Bax/Bcl-2 ratio was observed. Thus, the present study identified that ESCC tumors frequently expressed HO-1. Knockdown of HO-1 promoted apoptosis through activation of a ROS-mediated caspase apoptosis pathway.

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“…Peptide D[KLAKLAK]2 (KLA) was modified with 2, 3-dimethylmaleic anhydride (DMA) and combined with 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) to yield a DSPE-KLA-DMA (DKD) lipid, which, at tumor extracellular pH (~6.8), reversed the surface charge of liposomes (negative to positive), facilitating their internalization. In vitro studies proved that pH-sensitive-modified liposomes exhibited improved efficacy in treating drug-resistant lung cancer A549/Taxol cells compared to conventional therapy [82].…”

Section: Multifunctional Liposomes For Enhanced Intracellular Deliverymentioning

confidence: 99%

Liposomal Nanoformulations as Current Tumor-Targeting Approach to Cancer Therapy

Porfire¹,

Achim²,

Tefas³

et al. 2017

Liposomes

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The liposomes present great potential for applications in targeted delivery of chemotherapeutics in the treatment of cancer. The use of liposomal drug carriers as vehicles for targeting of chemotherapeutic agents to tumor tissues is based on their advantages over other dosage forms, represented by their low systemic toxicity, their bioavailability, and their possibility to enhance the solubility of different chemotherapeutic agents, due to the ability to encapsulate both hydrophilic and lipophilic drugs. They enhance the therapeutic index of anticancer drugs by increasing the drug concentration in tumor cells through tumor targeting. The available approaches used for tumor targeting using liposomes are passive targeting, active targeting, and triggered drug release. The most advanced targeting strategies proposed for cancer treatment are the development of multifunctional liposomes, having combined targeting mechanism. In this chapter, the tumor-targeting mechanisms are described in detail as well as the possibilities to design the targeted liposomal nanocarrier in order to reach the desired target in the body and minimizing the off-target effects. Moreover, the current status of preclinical and clinical evaluation is highlighted.

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Overcoming drug-resistant lung cancer by paclitaxel loaded dual-functional liposomes with mitochondria targeting and pH-response

Cited by 267 publications

References 60 publications

Systemic Delivery of Tumor-Targeted Bax-Derived Membrane-Active Peptides for the Treatment of Melanoma Tumors in a Humanized SCID Mouse Model

Systemic Delivery of Tumor-Targeted Bax-Derived Membrane-Active Peptides for the Treatment of Melanoma Tumors in a Humanized SCID Mouse Model

Evaluation of HO-1 expression, cellular ROS production, cellular proliferation and cellular apoptosis in human esophageal squamous cell carcinoma tumors and cell lines

Liposomal Nanoformulations as Current Tumor-Targeting Approach to Cancer Therapy

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