Folic Acid-Targeted Etoposide Cubosomes for Theranostic Application of Cancer Cell Imaging and Therapy

Tian, Yong; Li, Jianchun; Zhu, Jinxiu; Zhu, Na; Zhang, Hongmin; Liang, Lili; Sun, Lingyi

doi:10.12659/msm.904683

Cited by 50 publications

(25 citation statements)

References 41 publications

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“… 23 The formulated thymoquinone loaded cubosomes particle size was of nanometric size similar to those reported in literature. 32 In Tian et al study, etoposide loaded-cubosomes had particle sizes of 173.6 ± 1.60 nm with 0.174 PDI value; the consistent low PDI in various studies demonstrated the ability of cubosomes dispersion to maintain homogeneity, yet the observed particle size difference is clarified by the modified formulation and process parameters. This is further evident by Swarnakar et al study which highlighted the effect of the formulation factors as well as the process parameters as the surfactant nature and its concentration, drug loading as well as the sonication time on the cubosomes particle size and PDI.…”

Section: Discussionmentioning

confidence: 91%

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Anticancer Activity of Thymoquinone Cubic Phase Nanoparticles Against Human Breast Cancer: Formulation, Cytotoxicity and Subcellular Localization

Mehanna¹,

Sarieddine²,

Alwattar³

et al. 2020

IJN

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Introduction: Triple negative breast cancer is an aggressive disorder which accounts for at least 15% of breast cancer diagnosis and a high percentage of breast cancer morbidity, hence intensive research efforts are focused on the development of effective therapies to overcome the disease. Thymoquinone (TQ), the bioactive constituent of Nigella sativa, exhibits anticancer activity, yet its translation to the clinic is hindered by its poor bioavailability and lack of quantification method in blood and tissues. To overcome these limitations, cubosomes were utilized for the encapsulation and delivery of this anticancer molecule. Methods: Thymoquinone loaded cubosomes were prepared through the emulsification homogenization method. The physicochemical characteristics, including particle size, zeta potential, morphology and entrapment efficiency, were studied. Moreover, the in vitro antitumor activity was tested on breast cancer cell lines (MCF-7 and MDA-MB-231) and compared to non-tumorigenic cell line (MCF-10A). Subcellular localization, cellular uptake and apoptotic effects of the formulations were assessed. Results: The results revealed that the TQ loaded cubosomal formulation exhibited a mean particle size of 98.0 ± 4.10 nm with narrow unimodal distribution. The high entrapment efficiency (96.60 ± 3.58%) and zeta potential (31.50 ±4.20 mV) conceived the effectiveness of this nanosystem for TQ encapsulation. Cell viability in both breast cancer cell lines demonstrated a dose-dependent decrease in response to treatment with free TQ or TQ-loaded cubosomes, with enhanced antitumor activity upon treating with the latter formulation. A significant increase in apoptotic bodies and cleaved caspase 3 was observed upon treatment of MDA-MB-231 cells with either TQ or TQ-loaded cubosomes. Localization and trafficking studies unveiled that cubosomes accumulate in the cytoplasm of the studied breast cancer cell lines. Discussion: Our results show that thymoquinone encapsulation in cubosomal nanoparticles provides a promising anticancer drug delivery system with the ability to label, detect and subsequently trace it within the human cells.

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Section: Discussionmentioning

confidence: 91%

“…The amount of thymoquinone in the recovery chamber was quantified by high pressure liquid chromatography (HPLC). The entrapment efficiency of thymoquinone was calculated as follows: 32 %EE ¼ ðTotal weight of TQ added À Weight of unentrapped TQÞ=Total weight of TQÞ X 100…”

Section: Entrapment Efficiency Of Thymoquinone In Lcnpsmentioning

confidence: 99%

Anticancer Activity of Thymoquinone Cubic Phase Nanoparticles Against Human Breast Cancer: Formulation, Cytotoxicity and Subcellular Localization

Mehanna¹,

Sarieddine²,

Alwattar³

et al. 2020

IJN

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“…Targeting therapy has become the new therapeutic approach for cancer treatment. This involves delivery of the anticancer drugs at the specific site without any cytotoxic effects on other tissues or organs 43 , where the effects of cancer may be reduced/reversed. The concept and development of lipid nanovehicles have been originated in 1970s, which are in the mould of continuous modification until today.…”

Section: Discussionmentioning

confidence: 99%

Theranostic combinatorial drug-loaded coated cubosomes for enhanced targeting and efficacy against cancer cells

et al. 2020

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Cubosomes, a product of nanobioengineering, are self-structured lipid nanoparticles that act like drug-loaded theranostic probes. Here, we describe a simple method for the preparation of combinatorial drug-loaded cubosomes with, proof-of-principle, therapeutic effect against cancer cells, along with diagnostic capabilities. Anticancer drugs cisplatin and paclitaxel were loaded in the cubosomes in combination. The cubosomes were coated with a layer of poly-Ɛ-lysine, which helped avoid the initial burst release of drug and allowed for a slow and sustained release for better efficacy. Cubosomes were imaged by transmission electron microscope, and their dispersion analyzed in vitro by differential scanning calorimetric and X-ray diffractogram studies. The microscopic images depicted spherical polyangular structures, which are easily distinguishable. The analyses revealed that the drug is uniformly dispersed all through the cubosomes. Further characterization was carried out by zeta-potential measurement, in vitro release, and entrapment efficiency studies. The in vitro studies established that the coating of cubosomes successfully reduced the burst release of drugs initially and confirmed a slow, sustained release over increased time. Comparative cytotoxicity of coated, uncoated, and blank cubosomes was evaluated, using human hepatoma HepG2 cell line, and the formulations were found to be entirely nontoxic, similar to the blank ones. The therapeutic efficiency of the cubosomes against HeLa cells was confirmed by the impedance measurement and fluorescent imaging. Furthermore, the reduction in impedance in cells treated with coated combinatorial cubosomes proved the impairment of HeLa cells, as confirmed by fluorescence microscopy.

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“…carriers. 54,55 Another approach involves common modifications with specific ligands to protein receptors expressed on the surface of the cancer cells, typically folic acid ligands 56 or the tumor-homing and tumor-penetrating cyclic iRGD peptide, also due to its ability to increases the tumor vascular permeability. 57,58 Of course, the anti-cancer efficacy of the GMO-AT101 formulation requires further investigation in the GBM model in vivo.…”

Section: Encapsulated At101 Exhibits Stronger Cytotoxic Effects and Mmentioning

confidence: 99%

AT101-Loaded Cubosomes as an Alternative for Improved Glioblastoma Therapy

Flak

Adamski

Nowaczyk

et al. 2020

IJN

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Introduction: AT101, the R-(-)-enantiomer of the cottonseed-derived polyphenol gossypol, is a promising drug in glioblastoma multiforme (GBM) therapy due to its ability to trigger autophagic cell death but also to facilitate apoptosis in tumor cells. It does have some limitations such as poor solubility in water-based media and consequent low bioavailability, which affect its response rate during treatment. To overcome this drawback and to improve the anti-cancer potential of AT101, the use of cubosome-based formulation for AT101 drug delivery has been proposed. This is the first report on the use of cubosomes as AT101 drug carriers in GBM cells. Materials and Methods: Cubosomes loaded with AT101 were prepared from glyceryl monooleate (GMO) and the surfactant Pluronic F-127 using the top-down approach. The drug was introduced into the lipid prior to dispersion. Prepared formulations were then subjected to complex physicochemical and biological characterization. Results: Formulations of AT101-loaded cubosomes were highly stable colloids with a high drug entrapment efficiency (97.7%) and a continuous, sustained drug release approaching 35% over 72 h. Using selective and sensitive NMR diffusometry, the drug was shown to be efficiently bound to the lipid-based cubosomes. In vitro imaging studies showed the high efficiency of cubosomal nanoparticles uptake into GBM cells, as well as their marked ability to penetrate into tumor spheroids. Treatment of GBM cells with the AT101-loaded cubosomes, but not with the free drug, induced cytoskeletal rearrangement and shortening of actin fibers. The prepared nanoparticles revealed stronger in vitro cytotoxic effects against GBM cells (A172 and LN229 cell lines), than against normal brain cells (SVGA and HMC3 cell lines). Conclusion: The results indicate that GMO-AT101 cubosome formulations are a promising basic tool for alternative approaches to GBM treatment.

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Folic Acid-Targeted Etoposide Cubosomes for Theranostic Application of Cancer Cell Imaging and Therapy

Cited by 50 publications

References 41 publications

<p>Anticancer Activity of Thymoquinone Cubic Phase Nanoparticles Against Human Breast Cancer: Formulation, Cytotoxicity and Subcellular Localization</p>

<p>Anticancer Activity of Thymoquinone Cubic Phase Nanoparticles Against Human Breast Cancer: Formulation, Cytotoxicity and Subcellular Localization</p>

Theranostic combinatorial drug-loaded coated cubosomes for enhanced targeting and efficacy against cancer cells

<p>AT101-Loaded Cubosomes as an Alternative for Improved Glioblastoma Therapy</p>

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