Development and in vitro assessment of an anti-tumor nano-formulation

Holley, Claire K.; Kang, Yeon June; Kuo, Chung-Fan; Abidian, Mohammad Reza; Majd, Sheereen

doi:10.1016/j.colsurfb.2019.110481

Cited by 8 publications

(11 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Note that we previously demonstrated that only a small fraction of encapsulated C6 (≈5%) was released from PLGA NPs within the first three hours of incubation, confirming its suitability as a tracer for these NPs. [ 10 ] U87 and U251 cells were treated with either IL13‐conjugated or unconjugated PEG‐NPs, labeled with C6 (at 10 µg mL −1 of C6) for 3 h. As presented in Figure A–B, IL13‐PEG‐NPs showed higher cellular uptake as compared to the untargeted PEG‐NPs in both U251 and U87 glioma cells. For a more quantitative comparison, we measured the percentage of NPs uptaken by U251 cells, by harvesting these cells and releasing the entrapped C6, and measuring the fluorescent signal via spectrophotometry.…”

Section: Resultsmentioning

confidence: 99%

Tumor Targeted Delivery of an Anti‐Cancer Therapeutic: An In Vitro and In Vivo Evaluation

Kang

Holley

Abidian

et al. 2020

Adv Healthcare Materials

Self Cite

View full text Add to dashboard Cite

The limited effectiveness of current therapeutics against malignant brain gliomas has led to an urgent need for development of new formulations against these tumors. Chelator Dp44mT (di‐2‐pyridylketone‐4,4‐dimethyl‐3‐thiosemicarbazone) presents a promising candidate to defeat gliomas due to its exceptional anti‐tumor activity and its unique ability to overcome multidrug resistance. The goal of this study is to develop a targeted nano‐carrier for Dp44mT delivery to glioma tumors and to assess its therapeutic efficacy in vitro and in vivo. Dp44mT is loaded into poly(ethylene glycol) (PEG)ylated poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles (NPs) decorated with glioma‐targeting ligand Interlukin 13 (IL13). IL13‐conjugation enhanced the NP uptake by glioma cells and also improved their transport across an in vitro blood‐brain‐barrier (BBB) model. This targeted formulation showed an outstanding toxicity towards glioma cell lines and patient‐derived stem cells in vitro, with IC50 values less than 125 nM, and caused no significant death in healthy brain microvascular endothelial cells. In vivo, when tested on a xenograft mouse model, IL13‐conjugated Dp44mT‐NPs reduced the glioma tumor growth by ≈62% while their untargeted counterparts reduced the tumor growth by only ≈16%. Notably, this formulation does not cause any significant weight loss or kidney/liver toxicity in mice, demonstrating its great therapeutic potential.

show abstract

Section: Resultsmentioning

confidence: 99%

Tumor Targeted Delivery of an Anti‐Cancer Therapeutic: An In Vitro and In Vivo Evaluation

Kang

Holley

Abidian

et al. 2020

Adv Healthcare Materials

Self Cite

View full text Add to dashboard Cite

show abstract

“…have shown promise for the treatment of highly aggressive malignant tumors, for example, brain gliomas. 37 Deferoxamine, the most commonly used iron chelator approved by the FDA, 38 has recently been proposed as a potential therapeutic drug for patients with neuroblastoma, leukemia, prostate cancer, and hepatocellular carcinoma through specifically chelating iron in tumor cells. 39 However, DFO has an extremely short half-life of approximately 20-30 minutes in human plasma so that it must be infused continuously for 8-24 h per day for several days each week, which hampers its potential applications due to its arduous regimen for patients and low compliance.…”

Section: Iron Nanochelating Agentsmentioning

confidence: 99%

“…Nanotechnology‐based iron chelators have been extensively studied in cancer therapy 9 . Novel iron nanochelators based on di‐2‐pyridylketone 4,4‐dimethyl‐3‐thiosemicarbazone (Dp44mT) have shown promise for the treatment of highly aggressive malignant tumors, for example, brain gliomas 37 . Deferoxamine, the most commonly used iron chelator approved by the FDA, 38 has recently been proposed as a potential therapeutic drug for patients with neuroblastoma, leukemia, prostate cancer, and hepatocellular carcinoma through specifically chelating iron in tumor cells 39 .…”

Section: Iron‐based Nanotherapeutics For Cancer Therapymentioning

confidence: 99%

Nanomedicine targets iron metabolism for cancer therapy

et al. 2022

View full text Add to dashboard Cite

Iron is an essential element for cell proliferation and homeostasis by engaging in cell metabolism including DNA synthesis, cell cycle, and redox cycling; however, iron overload could contribute to tumor initiation, proliferation, metastasis, and angiogenesis. Therefore, manipulating iron metabolisms, such as using iron chelators, transferrin receptor 1 (TFR1) Abs, and cytotoxic ligands conjugated to transferrin, has become a considerable strategy for cancer therapy. However, there remain major limitations for potential translation to the clinic based on the regulation of iron metabolism in cancer treatment. Nanotechnology has made great advances for cancer treatment by improving the therapeutic potential and lowering the side‐effects of the proved drugs and those under various stages of development. Early studies that combined nanotechnology with therapeutic means for the regulation of iron metabolism have shown certain promise for developing specific treatment options based on the intervention of cancer iron acquisition, transportation, and utilization. In this review, we summarize the current understanding of iron metabolism involved in cancer and review the recent advances in iron‐regulatory nanotherapeutics for improved cancer therapy. We also envision the future development of nanotherapeutics for improved treatment for certain types of cancers.

show abstract

“…This approach is predicted to protect healthy tissues from the cytotoxic effects as the timing and place of the drug release can be controlled [36]. Encapsulating Dp44mT in PLGA nanoparticles enhanced its ability to induce apoptosis and improved its selectivity towards cancer cells [37].…”

Section: Reviewmentioning

confidence: 99%

Reversing oncogenic transformation with iron chelation

Abdelaal

Veuger

2021

Oncotarget

View full text Add to dashboard Cite

Cancer cells accumulate iron to supplement their aberrant growth and metabolism. Depleting cells of iron by iron chelators has been shown to be selectively cytotoxic to cancer cells in vitro and in vivo. Iron chelators are effective at combating a range of cancers including those which are difficult to treat such as androgen insensitive prostate cancer and cancer stem cells. This review will evaluate the impact of iron chelation on cancer cell survival and the underlying mechanisms of action. A plethora of studies have shown iron chelators can reverse some of the major hallmarks and enabling characteristics of cancer. Iron chelators inhibit signalling pathways that drive proliferation, migration and metastasis as well as return tumour suppressive signalling. In addition to this, iron chelators stimulate apoptotic and ER stress signalling pathways inducing cell death even in cells lacking a functional p53 gene. Iron chelators can sensitise cancer cells to PARP inhibitors through mimicking BRCAness; a feature of cancers trademark genomic instability. Iron chelators target cancer cell metabolism, attenuating oxidative phosphorylation and glycolysis. Moreover, iron chelators may reverse the major characteristics of oncogenic transformation. Iron chelation therefore represent a promising selective mode of cancer therapy.

show abstract

Development and in vitro assessment of an anti-tumor nano-formulation

Cited by 8 publications

References 35 publications

Tumor Targeted Delivery of an Anti‐Cancer Therapeutic: An In Vitro and In Vivo Evaluation

Tumor Targeted Delivery of an Anti‐Cancer Therapeutic: An In Vitro and In Vivo Evaluation

Nanomedicine targets iron metabolism for cancer therapy

Reversing oncogenic transformation with iron chelation

Contact Info

Product

Resources

About