Enhanced targeted delivery of adenine to hepatocellular carcinoma using glycyrrhetinic acid-functionalized nanoparticles in vivo and in vitro

Wu, Fei; Xue, Hantao; Li, Xiaocheng; Diao, Wenbin; Jiang, Bin; Wang, Weiyu; Yu, Wei; Bai, Jingkun; Wang, Yi; Lian, Bo; Feng, Weiguo; Sun, Tao; Qu, Mei-Hua; Zhao, Chunling; Wang, Yubing; Wu, Jingliang; Gao, Zhiqin

doi:10.1016/j.biopha.2020.110682

Cited by 23 publications

(5 citation statements)

References 43 publications

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“…A cell uptake study was performed for the qualitative estimation of the targeting ability of GA-HA-NPs and CLSM was used to observe the cellular localization of the GA-HA-NPs. To demonstrate the effect of GA-HA-NP targeting, receptor-mediated cellular uptake of FITC-GA-HA-NPs was studied in HepG2 cells and MCF-7 cells [negative for GA receptor (GA-R) expression] ( 36 ). Fluorescence images of the cells taken after 2 h of incubation with FITC-GA-HA-NPs are provided in Fig.…”

Section: Resultsmentioning

confidence: 99%

Preparation of docetaxel‑loaded, glycyrrhetinic acid‑modified nanoparticles and their liver‑targeting and antitumor activity

et al. 2021

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Liver cancer is one of the most common malignancies worldwide and poses a serious threat to human health. The most important treatment method, liver cancer chemotherapy, is limited due to its high toxicity and poor specificity. Targeted drug delivery systems have emerged as novel therapeutic strategies that deliver precise, substantial drug doses to target sites via targeting vectors and enhance the therapeutic efficacy. In the present study, glycyrrhetinic acid-modified hyaluronic acid (GA-HA) was used as a carrier for the model drug docetaxel (DTX) to prepare DTX-loaded GA-HA nanoparticles (DTX/GA-HA-NPs). The results indicated that the DTX/GA-HA-NPs exhibited high monodispersity (particle dispersity index, 0.209±0.116) and desirable particle size (208.73±5.0 nm) and zeta potential (-27.83±3.14 mV). The drug loading capacity and encapsulation efficiency of the NPs were 12.59±0.68 and 85.38±4.62%, respectively. Furthermore, it was determined that FITC-GA-HA was taken up by cells and distributed in the cytoplasm. DTX and DTX/GA-HA (just the DTX delivered by the nanoparticle) aggregated and altered the structure of cellular microtubules. Compared with DTX alone, DTX/GA-HA-NPs had a stronger inhibitory effect on HepG2 cell proliferation and promoted apoptosis of HepG2 cells. All experimental results indicated that DTX/GA-HA-NPs were successfully prepared and had liver-targeting and antitumor activities in vitro , which provided a foundation for future in vivo studies of the antitumor effects of DTX/GA-HA-NPs.

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Section: Resultsmentioning

confidence: 99%

Preparation of docetaxel‑loaded, glycyrrhetinic acid‑modified nanoparticles and their liver‑targeting and antitumor activity

et al. 2021

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“…[ 43 ] For example, adenine‐loaded nanoparticles were reported whose surface was modified with GA and HA (Ade/GA‐HA) for liver targeting. [ 44 ] As GA is a pentacyclic triterpenoid glycoside exhibiting hydrophobic characteristics, the water solubility concern was resolved by using hydrophilic HA, which is a CD44 receptor‐binding acid mucopolysaccharide. For in vitro imaging of HepG2 cells, HA was labeled with fluorescein isothiocyanate (FITC) to yield FITC‐labeled GA‐HA for incorporation into originally produced GA‐HA NPs.…”

Section: Fluorescent Prodrug Systems For Liver Cancermentioning

confidence: 99%

Cancer Cell‐Specific Fluorescent Prodrug Delivery Platforms

Kim

Chen

et al. 2023

Advanced Science

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Targeting cancer cells with high specificity is one of the most essential yet challenging goals of tumor therapy. Because different surface receptors, transporters, and integrins are overexpressed specifically on tumor cells, using these tumor cell-specific properties to improve drug targeting efficacy holds particular promise. Targeted fluorescent prodrugs not only improve intracellular accumulation and bioavailability but also report their own localization and activation through real-time changes in fluorescence. In this review, efforts are highlighted to develop innovative targeted fluorescent prodrugs that efficiently accumulate in tumor cells in different organs, including lung cancer, liver cancer, cervical cancer, breast cancer, glioma, and colorectal cancer. The latest progress and advances in chemical design and synthetic considerations in fluorescence prodrug conjugates and how their therapeutic efficacy and fluorescence can be activated by tumor-specific stimuli are reviewed. Additionally, novel perspectives are provided on strategies behind engineered nanoparticle platforms self-assembled from targeted fluorescence prodrugs, and how fluorescence readouts can be used to monitor the position and action of the nanoparticle-mediated delivery of therapeutic agents in preclinical models. Finally, future opportunities for fluorescent prodrug-based strategies and solutions to the challenges of accelerating clinical translation for the treatment of organ-specific tumors are proposed.

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“…Using the same DDS, Wu and coworkers [ 48 ] tried to target liver cancer cells with adenine (ADE), an anticancer agent able to induce cell arrest in the S phase in human hepatic carcinoma cells, leading to tumor cell proliferation arrest and subsequent cell apoptosis. Interestingly, data reported that GA-HA NPs were more efficient in targeting liver cancer cells than normal liver cells (due to the higher presence of GA receptors in tumor cells than in normal cells), leading the authors to hypothesize reduced drug side effects on normal tissues.…”

Section: Ga-functionalized Polymer-based Ddssmentioning

confidence: 99%

Recent Advances in Glycyrrhetinic Acid-Functionalized Biomaterials for Liver Cancer-Targeting Therapy

et al. 2022

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Liver cancer is one of the most common causes of cancer mortality worldwide. Chemotherapy and radiotherapy are the conventional therapies generally employed in patients with liver tumors. The major issue associated with the administration of chemotherapeutics is their high toxicity and lack of selectivity, leading to systemic toxicity that can be detrimental to the patient’s quality of life. An important approach to the development of original liver-targeted therapeutic products takes advantage of the employment of biologically active ligands able to bind specific receptors on the cytoplasmatic membranes of liver cells. In this perspective, glycyrrhetinic acid (GA), a pentacyclic triterpenoid present in roots and rhizomes of licorice, has been used as a ligand for targeting the liver due to the expression of GA receptors on the sinusoidal surface of mammalian hepatocytes, so it may be employed to modify drug delivery systems (DDSs) and obtain better liver or hepatocyte drug uptake and efficacy. In the current review, we focus on the most recent and interesting research advances in the development of GA-based hybrid compounds and DDSs developed for potential employment as efficacious therapeutic options for the treatment of hepatic cancer.

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Enhanced targeted delivery of adenine to hepatocellular carcinoma using glycyrrhetinic acid-functionalized nanoparticles in vivo and in vitro

Cited by 23 publications

References 43 publications

Preparation of docetaxel‑loaded, glycyrrhetinic acid‑modified nanoparticles and their liver‑targeting and antitumor activity

Preparation of docetaxel‑loaded, glycyrrhetinic acid‑modified nanoparticles and their liver‑targeting and antitumor activity

Cancer Cell‐Specific Fluorescent Prodrug Delivery Platforms

Recent Advances in Glycyrrhetinic Acid-Functionalized Biomaterials for Liver Cancer-Targeting Therapy

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