N-acetylaminogalactosyl-decorated biodegradable PLGA-TPGS copolymer nanoparticles containing emodin for the active targeting therapy of liver cancer

Dong, Huijuan; Wu, Guoyu; Xu, Hong; Zhang, Chenghong; Wang, Jiao; Gao, Meng; Pang, Yue; Zhang, Hou-Li; Zhang, Baojing; Tian, Ye; Li, Qingwei

doi:10.1080/21691401.2018.1455055

Cited by 22 publications

(20 citation statements)

References 35 publications

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“…Finding more appropriate drugs or delivery methods with lower cytotoxicity and fewer side effects are important tasks for HCC chemotherapy. 14,15 Alkaloids are organic compounds containing nitrogen that occur nature, most of which are basic, some of which are neutral (eg, colchicine) or even acidic (eg, theophylline, theobromine). A wide range of pharmacological properties and effects have been reported, such as antimalarial (eg, quinine), antiasthma (eg, ephedrine), anticancer (eg, homoharringtonine), cholinomimetic (eg, galantamine), vasodilatory (eg, vincristine), antiarrhythmic (eg, quinidine), analgesic (eg, morphine), antibacterial (eg, chelerythrine), and antihyperglycemic activities (eg, vincristine and vinblastine).…”

Section: Discussionmentioning

confidence: 99%

IGFBP-3 Is the Key Target of Sanguinarine in Promoting Apoptosis in Hepatocellular Carcinoma

Wang¹,

Wang²,

Li³

et al. 2020

CMAR

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Introduction: Chemotherapeutic treatment of hepatocellular carcinoma (HCC) has always been plagued by nonspecific and side effects. Plant extracts have potential anticancer capabilities with low cytotoxicity and few side effects, but their detailed mechanisms are still unclear, thus limiting their clinical applications. Methods: In this study, five plant extracts were chosen, their inhibition on HCC cell viability was compared by CCK-8 assay and sanguinarine (SAN) was selected. Then, wound healing assay, transwell assay, and apoptosis assay were carried out in Hep3B cells. Bioinformatics methods were performed and IGFBP-3 was predicted the targets of SAN in HCC. The mechanism of SAN regulating IGFBP-3 was explored using qRT-PCR, Western blotting, cell viability assay and apoptosis assay. Meanwhile, knockdown of IGFBP-3 were used by small interfering RNA (siRNA). Results: In five plant extracts, SAN inhibited the proliferation of HCC cell lines most considerably. In addition, apoptosis was promoted, and invasion and migration were inhibited in the Hep3B cell line by treatment with SAN at 2 μM. Bioinformatics indicated that SAN could affect HCC apoptosis through the TP53/IGFBP-3 pathway, and further verification experiments showed that SAN upregulated the expression of insulin-like growth factor binding protein-3 (IGFBP-3) in the Hep3B cell line; SAN also inhibited the expression of Bcl-2 and promoted the expression of BAX and caspase-3. After using siRNA to inhibit the expression of IGFBP-3, the effect of SAN was blocked. Conclusion: Our study further reveals a novel mechanism that IGFBP-3 is an important target of SAN, by upregulating expression of IGFBP-3, SAN promotes apoptosis in HCC. Plain Language SummaryChemotherapy for hepatocellular carcinoma has many side effects, while plant extracts have better advantages; thus, further clarification of the mechanism of plant extracts in HCC is urgently needed. Previous studies have suggested that sanguinarine elicits potential antitumor effects by promoting the apoptosis of cancer cells, but the specific mechanism is still unclear. This study found that sanguinarine can effectively promote the apoptosis of hepatocellular carcinoma cells, and IGFBP-3 is the key target for this effect. Further study on SAN could provide a new model for treating HCC.

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Section: Discussionmentioning

confidence: 99%

IGFBP-3 Is the Key Target of Sanguinarine in Promoting Apoptosis in Hepatocellular Carcinoma

Wang¹,

Wang²,

Li³

et al. 2020

CMAR

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“…Therefore, various strategies such as surface modification, newly synthesized and porous have been developed to improve the PLGA nanoparticles. 30,47,48 In recent years, many studies have found that TPGS has many unique characteristics, such as absorption enhancer, mucosal immune adjuvant, and multi-drug resistance reversal property. TPGS can also be used as precursor drugs, micelles, and liposomes to improve the solubility, permeability, and stability of the preparation; thus, achieving sustained, controlled release and targeting effects.…”

Section: Discussionmentioning

confidence: 99%

Co-Delivery of Docetaxel and Salinomycin to Target Both Breast Cancer Cells and Stem Cells by PLGA/TPGS Nanoparticles

Gao¹,

Liu²,

Xie³

et al. 2019

IJN

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Conventional chemotherapy is hampered by the presence of breast cancer stem cells (BCSCs). It is crucial to eradicating both the bulky breast cancer cells and BCSCs, using a combination of conventional chemotherapy and anti-CSCs drugs. However, the synergistic ratio of drug combinations cannot be easily maintained in vivo. In our previous studies, we demonstrated that the simultaneous delivery of two drugs via nanoliposomes could maintain the synergistic drug ratio for 12 h in vivo. However, nanoliposomes have the disadvantage of quick drug release, which makes it difficult to maintain the synergistic drug ratio for a long time. Herein, we developed a co-delivery system for docetaxel (DTX)-a first-line chemotherapy drug for breast cancer-and salinomycin (SAL)-an anti-BCSCs drug-in rigid nanoparticles constituted of polylactide-co-glycolide/D-alpha-tocopherol polyethylene glycol 1000 succinate (PLGA/TPGS). Methods: Nanoparticles loaded with SAL and DTX at the optimized ratio (NSD) were prepared by the nanoprecipitation method. The characterization, cellular uptake, and cytotoxicity of nanoparticles were investigated in vitro, and the pharmacokinetics, tissue distribution, antitumor and anti-CSCs activity of nanoparticles were evaluated in vivo. Results: We demonstrated that a SAL/DTX molar ratio of 1:1 was synergistic in MCF-7 cells and MCF-7-MS. Moreover, the enhanced internalization of nanoparticles was observed in MCF-7 cells and MCF-7-MS. Furthermore, the cytotoxicity of NSD against both MCF-7 cells and MCF-7-MS was stronger than the cytotoxicity of any single treatment in vitro. Significantly, NSD could prolong the circulation time and maintain the synergistic ratio of SAL to DTX in vivo for 24 h, thus exhibiting superior tumor targeting and anti-tumor activity compared to other treatments. Conclusion: Co-encapsulation of SAL and DTX in PLGA/TPGS nanoparticles could maintain the synergistic ratio of drugs in vivo in a better manner; thus, providing a promising strategy for synergistic inhibition of breast cancer.

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“…Nanoparticles were synthesized without any problem and liver targeting was achieved smoothly. Nanoparticles increased the antitumoral effect of emodin both in vivo and in vitro, performing it a possible choice for the treatment of primary liver cancer [ 120 ]. Emodin has been observed to stimulate mitochondrial dysfunction and apoptosis in HepG2 cells by upregulation of cyclophilin D. Expression of Cyclophilin D was effectively inhibited by the epidermal growth factor and N-acetyl-L-cysteine.…”

Section: Anticancer Activity Of Emodinmentioning

confidence: 99%

“…As a result, GalNAc-PLGA-TGPS nanoparticles exhibited a stronger antiproliferative effect on the HepG2 cell compared to the free emodin. Better active targeting and higher levels of inhibition of liver cancer cells were observed in mice [ 120 ]. It can be said that the newly synthesized GalNAc-PLGA-TPGS biomaterial has an important role in active targeting with the increase in asialoglycoprotein receptor expression.…”

Section: Nano-drug Delivery Strategies For Emodinmentioning

confidence: 99%

Is Emodin with Anticancer Effects Completely Innocent? Two Sides of the Coin

Akkol

Tatlı

Karatoprak

et al. 2021

Cancers

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Many anticancer active compounds are known to have the capacity to destroy pathologically proliferating cancer cells in the body, as well as to destroy rapidly proliferating normal cells. Despite remarkable advances in cancer research over the past few decades, the inclusion of natural compounds in researches as potential drug candidates is becoming increasingly important. However, the perception that the natural is reliable is an issue that needs to be clarified. Among the various chemical classes of natural products, anthraquinones have many biological activities and have also been proven to exhibit a unique anticancer activity. Emodin, an anthraquinone derivative, is a natural compound found in the roots and rhizomes of many plants. The anticancer property of emodin, a broad-spectrum inhibitory agent of cancer cells, has been detailed in many biological pathways. In cancer cells, these molecular mechanisms consist of suppressing cell growth and proliferation through the attenuation of oncogenic growth signaling, such as protein kinase B (AKT), mitogen-activated protein kinase (MAPK), HER-2 tyrosine kinase, Wnt/-catenin, and phosphatidylinositol 3-kinase (PI3K). However, it is known that emodin, which shows toxicity to cancer cells, may cause kidney toxicity, hepatotoxicity, and reproductive toxicity especially at high doses and long-term use. At the same time, studies of emodin, which has poor oral bioavailability, to transform this disadvantage into an advantage with nano-carrier systems reveal that natural compounds are not always directly usable compounds. Consequently, this review aimed to shed light on the anti-proliferative and anti-carcinogenic properties of emodin, as well as its potential toxicities and the advantages of drug delivery systems on bioavailability.

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N-acetylaminogalactosyl-decorated biodegradable PLGA-TPGS copolymer nanoparticles containing emodin for the active targeting therapy of liver cancer

Cited by 22 publications

References 35 publications

<p>IGFBP-3 Is the Key Target of Sanguinarine in Promoting Apoptosis in Hepatocellular Carcinoma</p>

<p>IGFBP-3 Is the Key Target of Sanguinarine in Promoting Apoptosis in Hepatocellular Carcinoma</p>

<p>Co-Delivery of Docetaxel and Salinomycin to Target Both Breast Cancer Cells and Stem Cells by PLGA/TPGS Nanoparticles</p>

Is Emodin with Anticancer Effects Completely Innocent? Two Sides of the Coin

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