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

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.

Chemoembolizing hepatocellular carcinoma with microsphere cored with arsenic trioxide microcrystal

“…The encapsulated microcrystal did not grow to large crystal but was stabilized within microsphere for sustained release (Figure 2(A,D)). The drug load was over 40%, which is 5-6 folds higher than that of reported ATO-microspheres (Zhou et al, 2005(Zhou et al, , 2012 and 4-20 folds higher than that of reported ATO-nanoparticles (Yang et al, 2009;Ellison et al, 2017;Lu et al, 2018;Hu et al, 2019;Lian et al, 2019). The encapsulation efficiency was 21.6%, which was at the similar level as previously reported studies (Lu et al, 2018;Lian et al, 2019).…”

“…Nanoparticles and microspheres are effective tools for sustained drug delivery and multiple studies on ATO nanoparticles and microspheres have shown improved antitumor effects (Zhou et al., 2005 ; Yang et al., 2009 ; Zhou et al., 2012 ; Kalepu & Nekkanti, 2015 ; Akhtar et al., 2017 ; Ellison et al., 2017 ; Lu et al., 2018 ; Duan et al., 2019 ; Hu et al., 2019 ; Lian et al., 2019 ; Wu et al., 2020 ). The drug loading of ATO and its releasing pattern in these particles are essential for therapeutic efficacy.…”

Red Blood Cell Membrane-Camouflaged Tedizolid Phosphate-Loaded PLGA Nanoparticles for Bacterial-Infection Therapy

“…For longer circulation and less immune recognition of nanoparticle drugs, diverse strategies are reported, such as modifying the surface with polyethyleneglycol (PEG) or cell-penetrating peptides [ 22 ]. Among them, red blood cell membrane (RBCM), as a natural bio-membrane extracted from red blood cells (RBCs), attracted extensive attention as a drug carrier [ 23 , 24 , 25 ]. RBCM is expected to help achieve a long circulation of drugs because of the presence of special proteins like CD47 contributing to lower uptake by macrophages [ 26 , 27 ].…”

Arsenic intoxication: general aspects and chelating agents

“…Therefore, the administration of these drugs should be evaluated when beneficial effects outweigh metal toxicity. The development of new strategies employing the use of As-based drugs in coated NPs systems provides a promising alternative for safe and effective tumor treatment (Lian et al 2019). However, consideration of the individual genetic predisposition, co-exposure to other toxins, diet, and particularly vulnerable neurological conditions should be taken carefully into account in prescribing these treatments ).…”