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

#### **Yumei Lian, Xuerui Wang, Pengcheng Guo, Yichen Li, Faisal Raza, Jing Su \* and Mingfeng Qiu \***

School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; lym-0517@sjtu.edu.cn (Y.L.); wangxuerui0303@163.com (X.W.); gpcedu@sjtu.edu.cn (P.G.); liyichen592@sjtu.edu.cn (Y.L.); faisalraza@sjtu.edu.cn (F.R.)

**\*** Correspondence: jingsu@sjtu.edu.cn (J.S.); mfqiu@sjtu.edu.cn (M.Q.); Tel.: +86-21-34204052 (M.Q.)

Received: 22 November 2019; Accepted: 18 December 2019; Published: 24 December 2019

**Abstract:** Arsenic trioxide (ATO) has a significant e ffect on the treatment of acute promyelocytic leukemia (APL) and advanced primary liver cancer, but it still faces severe side e ffects. 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 e fficiency 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 e ffects 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 e ffects. In brief, the developed RSANs system provides a promising alternative for ATO treatment safely and e ffectively.

**Keywords:** red blood cells membrane; arsenic trioxide; sodium alginate nanoparticles; reduce toxicity; anti-tumor
