An arsenic trioxide nanoparticle prodrug (ATONP) potentiates a therapeutic effect on an aggressive hepatocellular carcinoma model <i>via</i> enhancement of intratumoral arsenic accumulation and disturbance of the tumor microenvironment

Fu, Xin; Liang, Qing-Rong; Luo, Rong-guang; Li, Yanshu; Xiao, Xiaoping; Yu, Lulu; Shan, Wenzhe; Fan, Guang; Tang, Qun

doi:10.1039/c9tb00349e

Cited by 13 publications

(12 citation statements)

References 56 publications

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“…ATO can induce cell differentiation, inhibit apoptosis, and exert anti-tumor effect [4]. In recent years, research studies have confirmed the significant growth inhibition and apoptosis induction effect of ATO in solid tumors, such as liver cancer, breast cancer, stomach cancer, glioma and lung cancer [5][6][7][8][9][10][11]. At present, ATO injection has been employed clinically in the treatment of APL and advanced primary liver cancer.…”

Section: Introductionmentioning

confidence: 99%

Erythrocyte Membrane-Coated Arsenic Trioxide-Loaded Sodium Alginate Nanoparticles for Tumor Therapy

et al. 2019

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Arsenic trioxide (ATO) has a significant effect on the treatment of acute promyelocytic leukemia (APL) and advanced primary liver cancer, but it still faces severe side effects. Considering these problems, red blood cell membrane-camouflaged ATO-loaded sodium alginate nanoparticles (RBCM-SA-ATO-NPs, RSANs) were developed to relieve the toxicity of ATO while maintaining its efficacy. ATO-loaded sodium alginate nanoparticles (SA-ATO-NPs, SANs) were prepared by the ion crosslinking method, and then RBCM was extruded onto the surface to obtain RSANs. The average particle size of RSANs was found to be 163.2 nm with a complete shell-core bilayer structure, and the average encapsulation efficiency was 14.31%. Compared with SANs, RAW 264.7 macrophages reduced the phagocytosis of RSANs by 51%, and the in vitro cumulative release rate of RSANs was 95% at 84 h, which revealed a prominent sustained release. Furthermore, it demonstrated that RSANs had lower cytotoxicity as compared to normal 293 cells and exhibited anti-tumor effects on both NB4 cells and 7721 cells. In vivo studies further showed that ATO could cause mild lesions of main organs while RSANs could reduce the toxicity and improve the anti-tumor effects. In brief, the developed RSANs system provides a promising alternative for ATO treatment safely and effectively.

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Section: Introductionmentioning

confidence: 99%

Erythrocyte Membrane-Coated Arsenic Trioxide-Loaded Sodium Alginate Nanoparticles for Tumor Therapy

et al. 2019

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“…Therefore, to achieve the desired therapeutic effect, a large dose of ATO is required, but this high dose can lead to serious hepatotoxicity and nephrotoxicity [ 23 , 26 ]. Although some improved measures, such as intra-arterial infusion and arsenic efflux micropumps, have been used to minimize side effects, the overall survival of patients with HCC after ATO treatment has not been significantly prolonged [ 25 ]. Therefore, the development of a novel method is urgently needed to increase drug accumulation in residual HCC sites and increase its therapeutic efficacy while maintaining high biocompatibility.…”

Section: Introductionmentioning

confidence: 99%

Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression

et al. 2022

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Background Insufficient radiofrequency ablation (IRFA) can promote the local recurrence and distal metastasis of residual hepatocellular carcinoma (HCC), which makes clinical treatment extremely challenging. In this study, the malignant transition of residual tumors after IRFA was explored. Then, arsenic-loaded zeolitic imidazolate framework-8 nanoparticles (As@ZIF-8 NPs) were constructed, and their therapeutic effect on residual tumors was studied. Results Our data showed that IRFA can dramatically promote the proliferation, induce the metastasis, activate the epithelial–mesenchymal transition (EMT) and accelerate the angiogenesis of residual tumors. Interestingly, we found, for the first time, that extensive angiogenesis after IRFA can augment the enhanced permeability and retention (EPR) effect and enhance the enrichment of ZIF-8 nanocarriers in residual tumors. Encouraged by this unique finding, we successfully prepared As@ZIF-8 NPs with good biocompatibility and confirmed that they were more effective than free arsenic trioxide (ATO) in sublethal heat-induced cell proliferation suppression, apoptosis induction, cell migration and invasion inhibition, and EMT reversal in vitro. Furthermore, compared with free ATO, As@ZIF-8 NPs exhibited remarkably increased therapeutic effects by repressing residual tumor growth and metastasis in vivo. Conclusions This work provides a new paradigm for the treatment of residual HCC after IRFA. Graphical Abstract

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“…Among them, hepatocellular carcinoma (HCC) accounts for the vast majority with a high incidence and mortality rate. 1 , 2 Even though various clinically adopted HCC treatment methods have shown to be significant to ameliorate the disease, the use of chemotherapy is often associated with adverse side effects and limited therapeutic efficacy. 3 Thus, due to the limitation of chemotherapy, it is necessary to explore alternative strategies for the treatment of HCC.…”

Section: Introductionmentioning

confidence: 99%

Liposome-Coated Arsenic–Manganese Complex for Magnetic Resonance Imaging-Guided Synergistic Therapy Against Carcinoma

Jin¹,

Yang²,

Yang³

et al. 2021

IJN

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Purpose A liposome-coated arsenic–manganese complex, denoted as LP@MnAs x was constructed for the targeted delivery of arsenic trioxide (ATO) against carcinoma. Methods Arsenite, the prodrug of ATO, was encapsulated within a liposome via electrostatic interaction with the manganese ions. The as-prepared material was characterized with dynamic light scattering and transmission electron microscopy. The entrapment efficiency and drug loading of arsenic in the carrier were measured using inductively coupled plasma spectrometry. The in vitro release of arsenic was evaluated by using the dialysis bag method. Furthermore, the Fenton-like activity and in vitro cytodynamics research of LP@MnAs x were monitored in this work. And the cellular uptake study was used to investigate the in vitro entry mechanism. Furthermore, the cytotoxicity, cell apoptosis and cell cycle study were performed to evaluate the tumor-killing efficiency. Also, the pharmacokinetic and antitumor studies were investigated in HepG2 tumor-bearing nude mice. Results The as-prepared LP@MnAs x possessed a spherical morphology, uniformly distributed hydrodynamic diameter, and excellent drug-loading efficiency. LP@MnAs x displayed robust stability and sustained-release profile under physiological environments. LP@MnAs x could degrade with high sensitivity to the pH variation in the tumor microenvironment. As such, this could lead to a burst release profile of Mn 2+ and arsenite to achieve a synergistic therapy of chemodynamic therapy and chemotherapy. When compared to the carrier-free arsenate, in vitro experiments revealed that LP@MnAs x exhibited enhanced cellular uptake and tumor-killing efficiency. LP@MnAs x also demonstrated significantly enhanced tumor-specific in vivo distribution of arsenic, prolonged systemic circulation lifetime, and increased accumulation at the tumor site. Conclusion Based on the experimental results, LP@MnAs x is an ideal arsenic-based nanodelivery system, whereby it can improve the non-specific distribution of NaAsO 2 in vivo. Thus, this work can expand the research and application of arsenic trioxide against solid tumors.

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An arsenic trioxide nanoparticle prodrug (ATONP) potentiates a therapeutic effect on an aggressive hepatocellular carcinoma model via enhancement of intratumoral arsenic accumulation and disturbance of the tumor microenvironment

Abstract: An arsenic trioxide nanoparticle prodrug has a therapeutic effect on a transgenic liver cancer model by disturbing the tumor micro-environment and increasing the delivery efficiency.

Cited by 13 publications

References 56 publications

Erythrocyte Membrane-Coated Arsenic Trioxide-Loaded Sodium Alginate Nanoparticles for Tumor Therapy

Erythrocyte Membrane-Coated Arsenic Trioxide-Loaded Sodium Alginate Nanoparticles for Tumor Therapy

Augmented EPR effect post IRFA to enhance the therapeutic efficacy of arsenic loaded ZIF-8 nanoparticles on residual HCC progression

Liposome-Coated Arsenic–Manganese Complex for Magnetic Resonance Imaging-Guided Synergistic Therapy Against Carcinoma

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