Arsenic trioxide-loaded CalliSpheres: <i>In vitro</i> study of drug release and antitumor activity, and <i>in vivo</i> study of pharmacokinetics, treatment efficacy and safety in liver cancer

Duan, Xuhua; Zhao, Guiqiu; Han, Xinwei; Ren, Jianzhuang; Li, Hao; Chen, Pengfei; Wang, Manzhou; Ju, Shuguang

doi:10.3892/or.2021.8075

Cited by 7 publications

(2 citation statements)

References 32 publications

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“…Notably, CB is reported as an ideal drug carrier of apatinib, idarubicin, arsenic trioxide, etc. [ 10 , 41 , 42 ]. Combined with previous literatures, we concluded that the lidocaine/CalliSpheres ® composites were successfully prepared, and exhibited preliminary application potential as drug carriers.…”

Section: Resultsmentioning

confidence: 99%

One-step fabrication of lidocaine/CalliSpheres® composites for painless transcatheter arterial embolization

et al. 2022

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Background Transcatheter arterial embolization (TAE) is one of the first-line treatments for advanced hepatocellular cancer. The pain caused by TAE is a stark complication, which remains to be prevented by biomedical engineering methods. Methods Herein, a commercial embolic agent CalliSpheres® bead (CB) was functionally modified with lidocaine (Lid) using an electrostatic self-assembly technique. The products were coded as CB/Lid-n (n = 0, 5, 10, corresponding to the relative content of Lid). The chemical compositions, morphology, drug-loading, and drug-releasing ability of CB/Lid-n were comprehensively investigated. The biocompatibility was determined by hemolysis assay, live/dead cell staining assay, CCK8 assay, immunofluorescence (IHC) staining assay and quantitative real-time PCR. The thermal withdrawal latency (TWL) and edema ratio (ER) were performed to evaluate the analgesia of CB/Lid-n using a plantar inflammation model. A series of histological staining, including immunohistochemistry (IL-6, IL-10, TGF-β and Navi1.7) and TUNEL were conducted to reveal the underlying mechanism of anti-tumor effect of CB/Lid-n on a VX2-tumor bearing model. Results Lid was successfully loaded onto the surface of CalliSpheres® bead, and the average diameter of CalliSpheres® bead increased along with the dosage of Lid. CB/Lid-n exhibited desirable drug-loading ratio, drug-embedding ratio, and sustained drug-release capability. CB/Lid-n had mild toxicity towards L929 cells, while triggered no obvious hemolysis. Furthermore, CB/Lid-n could improve the carrageenan-induced inflammation response micro-environment in vivo and in vitro. We found that CB/Lid-10 could selectively kill tumor by blocking blood supply, inhibiting cell proliferation, and promoting cell apoptosis. CB/Lid-10 could also release Lid to relieve post-operative pain, mainly by remodeling the harsh inflammation micro-environment (IME). Conclusions In summary, CB/Lid-10 has relatively good biocompatibility and bioactivity, and it can serve as a promising candidate for painless transcatheter arterial embolization.

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Section: Resultsmentioning

confidence: 99%

One-step fabrication of lidocaine/CalliSpheres® composites for painless transcatheter arterial embolization

et al. 2022

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“…Our previous studies have confirmed that As 2 O 3 inhibits tumor growth, angiogenesis, and metastasis and has an anti-tumor effect on HCC. [17][18][19] As 2 O 3 induces apoptosis by generating reactive oxygen species, destroying mitochondrial transmembrane potential, downregulating Bcl-2, and activating caspase-3. In addition, reactive oxygen species are known to induce immunogenic tumor cell death.…”

Section: Introductionmentioning

confidence: 99%

Nrf2-siRNA Enhanced the Anti-Tumor Effects of As2O3 in 5-Fluorouracil-Resistant Hepatocellular Carcinoma by Inhibiting HIF-1α/HSP70 Signaling

Duan¹,

Xu²,

Li³

et al. 2022

JHC

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Chemoresistance is a major factor contributing to the failure of cancer treatment. The conventional chemotherapy agent 5-fluorouracil (5-FU) has been used for cancer treatment for decades. However, its use is limited in the treatment of hepatocellular carcinoma (HCC) due to acquired resistance. Nrf2 (NF-E2-related factor 2) is known to be associated with drug resistance across a wide range of cancer types. Also, since arsenic trioxide (As 2 O 3 ) showed antitumor effects on HCC, the purpose of this study was to determine whether As 2 O 3 and Nrf2-siRNA could inhibit HCC synergistically. Methods: We generated two separate 5-FU-resistant HCC cell lines (SNU-387/5-FU and Hep3B/5-FU). Western blotting was used to determine protein levels. An efficient lentiviral delivery system was used to establish stable knockdown or overexpression of Nrf2 and HIF-1α. In vitro and in vivo analyses of the effects of Nrf2 gene knockdown and As 2 O 3 on 5-FU-resistant HCC cells were conducted. Results: The expression of Nrf2 was higher in the 5-FU-resistant HCC cell lines than in the parental cell lines. When coupled with Nrf2 knockdown, As 2 O 3 treatment significantly decreased 5-FU-resistant SNU-387 and Hep3B cell viability, migration, and invasion, inactivated HIF-1α/HSP70 signaling, inhibited anti-apoptotic B-cell lymphoma (Bcl-2) activity, and increased the expression of proapoptotic Bcl-2-associated X protein (BAX) along with caspase-3. The synergistic effect was also confirmed using a 5-FU-resistant Hep3B mouse xenograft model in vivo. Conclusion: Nrf2 knockdown could improve the effect of As 2 O 3 on reversing drug resistance in 5-FU-resistant HCC cells.

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Thiolated chitosan nanoparticles for stable delivery and smart release of As2O3 for liver cancer through dual actions

Song

et al. 2023

Carbohydrate Polymers

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Arsenic trioxide-loaded CalliSpheres: In vitro study of drug release and antitumor activity, and in vivo study of pharmacokinetics, treatment efficacy and safety in liver cancer

Cited by 7 publications

References 32 publications

One-step fabrication of lidocaine/CalliSpheres® composites for painless transcatheter arterial embolization

One-step fabrication of lidocaine/CalliSpheres® composites for painless transcatheter arterial embolization

Nrf2-siRNA Enhanced the Anti-Tumor Effects of As2O3 in 5-Fluorouracil-Resistant Hepatocellular Carcinoma by Inhibiting HIF-1α/HSP70 Signaling

Thiolated chitosan nanoparticles for stable delivery and smart release of As2O3 for liver cancer through dual actions

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