Synthesis and anti-tumor activity study of water-soluble PEG-celastrol coupling derivatives as self-assembled nanoparticles

Shan, Wei‐Guang; Wang, Han-Guang; Wu, Rui; Zhan, Zha‐Jun; Ma, Lie‐Feng

doi:10.1016/j.bmcl.2019.01.042

Cited by 10 publications

(7 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The A549 cell absorption rate increased by 5.8 times, which made it higher cell uptake, stronger induction of apoptosis and antiproliferation activity compared with celastrol. In another study, Shan and colleagues (Shan et al, 2019) studied celastrol derivatives by combining carboxyl groups on C-20 with PEG covalent bonds, the compound (13) can form micelles in water, which greatly improve the stability of celastrol. At the same time, through the experiment of A549 xenograft nude mice, it was proved that compound (13) has higher activity and safety than celastrol.…”

Section: Increase Stability To Enhance Antitumor Effectsmentioning

confidence: 99%

“…Moreover, by adjusting the release response mechanism and release rate of drugs under different stimuli, the nanocarriers can control the sequence and time schedule of drug combination therapy, so as to achieve more accurate drug delivery process and improve the effect and specificity of combined action . The drug release behavior can be realized in different stimulant responses in tumor therapy, such as pH (Wang et al, 2017), hypoxia (Kumari et al, 2020), reduction (Xie and Liu, 2020), enzyme (Shan et al, 2019), temperature (Jommanee et al, 2018), ultrasound (Xia et al, 2018), etc.…”

Section: Taking Advantage Of Analogs Of Celastrolmentioning

confidence: 99%

See 1 more Smart Citation

Celastrol: A Review of Useful Strategies Overcoming its Limitation in Anticancer Application

Shi

et al. 2020

Front. Pharmacol.

116

View full text Add to dashboard Cite

Celastrol, a natural bioactive ingredient derived from Tripterygium wilfordii Hook F, exhibits significant broad-spectrum anticancer activities for the treatment of a variety of cancers including liver cancer, breast cancer, prostate tumor, multiple myeloma, glioma, etc. However, the poor water stability, low bioavailability, narrow therapeutic window, and undesired side effects greatly limit its clinical application. To address this issue, some strategies were employed to improve the anticancer efficacy and reduce the side-effects of celastrol. The present review comprehensively focuses on the various challenges associated with the anticancer efficiency and drug delivery of celastrol, and the useful approaches including combination therapy, structural derivatives and nano/micro-systems development. The specific advantages for the use of celastrol mediated by these strategies are presented. Moreover, the challenges and future research directions are also discussed. Based on this review, it would provide a reference to develop a natural anticancer compound for cancer treatment.

show abstract

Section: Increase Stability To Enhance Antitumor Effectsmentioning

confidence: 99%

Section: Taking Advantage Of Analogs Of Celastrolmentioning

confidence: 99%

Celastrol: A Review of Useful Strategies Overcoming its Limitation in Anticancer Application

Shi

et al. 2020

Front. Pharmacol.

116

View full text Add to dashboard Cite

show abstract

“…In LNCaP tumor xenograft mice, CLT-loaded nanoparticles treated with RES saturation outperformed free CLT and CLT-loaded nanoparticles alone in terms of antitumor efficacy. With the aim of improving the water-solubility and drug-ability of CLT, Shan et al 80 synthesized a sequence of PEG-CLT derivatives (PEGCs) by conjugating various types of PEGs to the carboxyl of CLT through the Mitsunobu reaction. Interestingly, among these PEGCs, DC1000 obtained by conjugating PEG with a molecular weight of 1000 and CLT could be easily dispersed in water to form self-assembled nanoparticles.…”

Section: Polymeric Nanoparticlesmentioning

confidence: 99%

Recent progress in nanotechnology-based drug carriers for celastrol delivery

2021

View full text Add to dashboard Cite

show abstract

“…[33][34][35] Therefore, the development of new drug delivery technologies to overcome the serious adverse effects and improve the therapeutic outcomes is critical for the clinical application of CEL. [36][37][38][39][40] To this end, we herein report the preparation of a novel type of CEL self-stabilized nanoparticles (CEL-NPs) for the effective treatment of melanoma. The CEL-NPs consisting of CEL and methoxyl poly (ethylene glycol)-b-poly (L-lysine) (mPEG-PLL) polymer were prepared by a facile "in situ chemical conjugation-induced self-assembly" strategy.…”

Section: Introductionmentioning

confidence: 99%

<p>Celastrol Self-Stabilized Nanoparticles for Effective Treatment of Melanoma</p>

Li¹,

Jia²,

Zhang³

et al. 2020

IJN

View full text Add to dashboard Cite

Background: Celastrol (CEL), a triterpene extracted from the Chinese herb tripterygium wilfordii, has been reported to have profound anticancer activities. However, poor water solubility and high side toxicities have severely restricted the clinical applications of CEL. Purpose: We proposed a facile "in situ drug conjugation-induced self-assembly" strategy to prepare CEL-loaded nanoparticles (CEL-NPs) that exhibited enhanced antitumor activity against melanoma. Methods: First, the CEL was chemically conjugated onto a methoxyl poly(ethylene glycol)b-poly(L-lysine) (mPEG-PLL) backbone, resulting in the conversion of the double hydrophilic mPEG-PLL polymer into an amphiphilic polymer prodrug, mPEG-PLL/CEL. The obtained mPEG-PLL/CEL could self-assemble into stable micelles in aqueous solution due to the hydrophobic association of CEL moieties in the side chains and the possible electrostatic interaction between the carboxyl group in CEL and the residue amine group in the PLL segment. Thus, the obtained mPEG-PLL/CEL nanoparticles were named CEL self-stabilized nanoparticles (CEL-NPs), which were then characterized by dynamic light scattering and transmission electron microscopy. Furthermore, the antitumor effects of the CEL-NPs were investigated by an MTT assay in vitro and in a B16F10 tumor-bearing mice model. Results: The CEL-NPs exhibited sustained drug release behavior and were effectively endocytosed by B16F10 cells. Furthermore, the in vivo antitumor evaluation demonstrated that the CEL-NPs had remarkably higher tumor growth inhibition rates and lower systemic side effects than free CEL. Conclusion: In summary, our present work not only demonstrates the generation of stable CEL-loaded nanoparticles for the efficient treatment of melanoma but also describes a general way to prepare drug self-stabilized nanomedicine for anticancer therapy.

show abstract

Synthesis and anti-tumor activity study of water-soluble PEG-celastrol coupling derivatives as self-assembled nanoparticles

Cited by 10 publications

References 26 publications

Celastrol: A Review of Useful Strategies Overcoming its Limitation in Anticancer Application

Celastrol: A Review of Useful Strategies Overcoming its Limitation in Anticancer Application

Recent progress in nanotechnology-based drug carriers for celastrol delivery

<p>Celastrol Self-Stabilized Nanoparticles for Effective Treatment of Melanoma</p>

Contact Info

Product

Resources

About