Combination of magnetic targeting with synergistic inhibition of NF-κB and glutathione via micellar drug nanomedicine enhances its anti-tumor efficacy

Elhasany, Kholod A.; Khattab, Sherine N.; Bekhit, Adnan A.; Ragab, Doaa; Abdulkader, M; Zaky, Amira; Helmy, Maged W.; Ashour, Hayam M. A.; Teleb, Mohamed; Haiba, Nesreen S.; Elzoghby, Ahmed O.

doi:10.1016/j.ejpb.2020.08.004

Cited by 23 publications

(21 citation statements)

References 58 publications

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“…Specifically, SPIONtagged amphiphilic zein-chondroitin sulfate micelles were used to achieve simultaneous CD44-tumor-targeted drug delivery of celastrol and sulfasalazine along with MRI. The combination nanoplatform showed highest efficacy compared to non-targeted and free drug treatment groups confirming its superiority (Elhasany et al, 2020). Furthermore, folate receptor-targeted liposomes carrying combination of celastrol and irinotecan have also been reported for lung and breast cancer treatment (Soe et al, 2018).…”

Section: Celastrol Nanoformulations and Their Therapeutic Applications Cancermentioning

confidence: 76%

“…NF-κB inhibition is the most commonly reported pharmacological mechanism of celastrol's anti-cancer activity FIGURE 1 | Structure of celastrol, potential therapies, challenging issues, and schematic representation of various celastrol nanoformulations [modified from Desai et al (2012)]. (Elhasany et al, 2020). Celastrol also inhibits M2-like polarized tumor-associated macrophages that are involved in tumor metastasis.…”

Section: Celastrol Nanoformulations and Their Therapeutic Applications Cancermentioning

confidence: 99%

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Nanotechnology-Based Celastrol Formulations and Their Therapeutic Applications

et al. 2021

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Celastrol (also called tripterine) is a quinone methide triterpene isolated from the root extract of Tripterygium wilfordii (thunder god vine in traditional Chinese medicine). Over the past two decades, celastrol has gained wide attention as a potent anti-inflammatory, anti-autoimmune, anti-cancer, anti-oxidant, and neuroprotective agent. However, its clinical translation is very challenging due to its lower aqueous solubility, poor oral bioavailability, and high organ toxicity. To deal with these issues, various formulation strategies have been investigated to augment the overall celastrol efficacy in vivo by attempting to increase the bioavailability and/or reduce the toxicity. Among these, nanotechnology-based celastrol formulations are most widely explored by pharmaceutical scientists worldwide. Based on the survey of literature over the past 15 years, this mini-review is aimed at summarizing a multitude of celastrol nanoformulations that have been developed and tested for various therapeutic applications. In addition, the review highlights the unmet need in the clinical translation of celastrol nanoformulations and the path forward.

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Section: Celastrol Nanoformulations and Their Therapeutic Applications Cancermentioning

confidence: 76%

Section: Celastrol Nanoformulations and Their Therapeutic Applications Cancermentioning

confidence: 99%

Nanotechnology-Based Celastrol Formulations and Their Therapeutic Applications

et al. 2021

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“…DSC is an analytical technique that measures thermal properties (temperatures and heat flows) of a given formulation in relation to any transition in it as a function of temperature and time under a controlled atmosphere. The DSC thermogram of EXE-loaded LCNPs F2 showed the disappearance of the endothermic peak of EXE at 85.6°C, confirming the entrapment of EXE and suggesting that entrapped EXE was molecularly dispersed in an amorphous state into the GMO ( Figure 4B ) ( Elhasany et al, 2020 ). Moreover, disappearance of the MTX endothermic characteristic peak at 123.7°C in the thermogram of MTX–Lf conjugate F3 indicates the successful conjugation between MTX and Lf ( Figure 4B ) ( Kamel et al, 2019 ).…”

Section: Resultsmentioning

confidence: 87%

Methotrexate-Lactoferrin Targeted Exemestane Cubosomes for Synergistic Breast Cancer Therapy

et al. 2022

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While the treatment regimen of certain types of breast cancer involves a combination of hormonal therapy and chemotherapy, the outcomes are limited due to the difference in the pharmacokinetics of both treatment agents that hinders their simultaneous and selective delivery to the cancer cells. Herein, we report a hybrid carrier system for the simultaneous targeted delivery of aromatase inhibitor exemestane (EXE) and methotrexate (MTX). EXE was physically loaded within liquid crystalline nanoparticles (LCNPs), while MTX was chemically conjugated to lactoferrin (Lf) by carbodiimide reaction. The anionic EXE-loaded LCNPs were then coated by the cationic MTX–Lf conjugate via electrostatic interactions. The Lf-targeted dual drug-loaded LCNPs exhibited a particle size of 143.6 ± 3.24 nm with a polydispersity index of 0.180. It showed excellent drug loading with an EXE encapsulation efficiency of 95% and an MTX conjugation efficiency of 33.33%. EXE and MTX showed synergistic effect against the MCF-7 breast cancer cell line with a combination index (CI) of 0.342. Furthermore, the Lf-targeted dual drug-loaded LCNPs demonstrated superior synergistic cytotoxic activity with a combination index (CI) of 0.242 and a dose reduction index (DRI) of 34.14 and 4.7 for EXE and MTX, respectively. Cellular uptake studies demonstrated higher cellular uptake of Lf-targeted LCNPs into MCF-7 cancer cells than non-targeted LCNPs after 4 and 24 h. Collectively, the targeted dual drug-loaded LCNPs are a promising candidate offering combinational hormonal therapy/chemotherapy for breast cancer.

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“…Elhasany et al 126 designed a multi-functional micellar nanomedicine (SPIONs/CS-loaded SFZ/zein-ChS PMs) by encapsulating CLT and sulfasalazine (SFZ), and oleic acidcapped superparamagnetic iron oxide nanoparticles (SPIONs) into the hydrophobic core of zein-chondroitin sulphate (zein-ChS) micelles. The combination of magnetic targeting and the active targeting effect of ChS increased the uptake of the micelles by MCF-7 cancer cells, resulting in a higher cytotoxicity against MCF-7 breast cancer cells.…”

Section: Biomaterials Science Reviewmentioning

confidence: 99%