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

Yumei Lian,Pengcheng Guo,Jing Su,Faisal Raza,Mingfeng Qiu,Xuerui Wang,Yichen Li

doi:10.3390/pharmaceutics12010021

Yumei Lian, Pengcheng Guo + Show 5 more

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https://doi.org/10.3390/pharmaceutics12010021

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Journal: Pharmaceutics	Publication Date: Dec 24, 2019
Citations: 35	License type: CC BY 4.0

Affiliation: Shanghai Jiao Tong University

Abstract

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.

Highlights

IntroductionArsenic trioxide (ATO) is the main active ingredient of traditional Chinese medicine (TCM)
Arsenic trioxide (ATO) is the main active ingredient of traditional Chinese medicine (TCM)Arsenic
In the 1970s, it was first applied to acute promyelocytic leukemia (APL) with significant efficacy [1] and was approved by the National Medical Products Administration (NMPA) and Food and Drug Administration (FDA) as a first-line treatment for APL in 1999 and 2000, respectively [2,3]

Summary

Introduction

Arsenic trioxide (ATO) is the main active ingredient of traditional Chinese medicine (TCM). ATO can induce cell differentiation, inhibit apoptosis, and exert anti-tumor effect [4]. 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]. ATO injection has been employed clinically in the treatment of APL and advanced primary liver cancer. The unique physicochemical properties of ATO allow it to be rapidly cleared from blood, and it requires daily administration during clinical treatment. Considering the potent toxicity of ATO, increasing the dose of ATO will increase the systemic toxicity and cause damage to the liver, kidney, heart, and peripheral nerve [12,13,14]

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