Synergistic chemotherapeutic effect of sorafenib-loaded pullulan-Dox conjugate nanoparticles against murine breast carcinoma.
pH-Sensitive pullulan-doxorubicin conjugates encapsulating sorafenib (P-Dox/S) nanoparticles were developed as a synergistic combinatorial delivery system against murine breast carcinoma. The nanoparticles can encapsulate Dox and sorafenib with ultra-high loading capacity (65.34 wt%) through chemical conjugation and physical loading, whereas can remain stable under physiological conditions and gradually release Dox and sorafenib with the decreasing pH. These conjugates can be effectively internalized and clearly suppress 4T1 cell growth in vitro. Furthermore, research data of in vivo animal models revealed that the synergistic combinatorial P-Dox/S nanoparticles heavily accumulated in solid tumor tissue sites to maximize therapeutic efficacy; they also significantly inhibited solid tumor growth, even remarkably reduced solid tumor volume in comparison to the initial volume, and obviously diminished adverse effects. The anti-tumor therapeutic effect obviously outperformed the delivery of combinational chemotherapy of free drugs or single drug-loaded P-Dox nanoparticles at the same concentration. These promising results indicate the high-efficiency synergistic chemotherapeutic effects of these nanoparticles. Combinational chemotherapy using P-Dox/S nanoparticles has important potential in the clinical treatment of malignancy for overcoming drug resistance and heterogeneity.
National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China. sunyong8702@scu.edu.cn fan_yujiang@scu.edu.cn.
Junhui
J
Sui
National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China. sunyong8702@scu.edu.cn fan_yujiang@scu.edu.cn.
Yani
Y
Cui
National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China. sunyong8702@scu.edu.cn fan_yujiang@scu.edu.cn.
Hanxu
H
Cai
National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China. sunyong8702@scu.edu.cn fan_yujiang@scu.edu.cn.
Shaoquan
S
Bian
National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China. sunyong8702@scu.edu.cn fan_yujiang@scu.edu.cn.
Zhiyi
Z
Xu
Cancer Center, West China hospital, Sichuan University, 37 Guoxue Lane, Chengdu 610064, China.
Ling
L
Zhou
National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China. sunyong8702@scu.edu.cn fan_yujiang@scu.edu.cn.
Yong
Y
Sun
National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China. sunyong8702@scu.edu.cn fan_yujiang@scu.edu.cn.
Jie
J
Liang
National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China. sunyong8702@scu.edu.cn fan_yujiang@scu.edu.cn.
Yujiang
http://orcid.org/0000-0002-4950-9399
Y
Fan
National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China. sunyong8702@scu.edu.cn fan_yujiang@scu.edu.cn.
Xingdong
X
Zhang
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D005260:Female; D005936:Glucans / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D000077157:Sorafenib
D000970:Antineoplastic Agents; D005936:Glucans; D010671:Phenylurea Compounds; D009536:Niacinamide; D004317:Doxorubicin; C009109:pullulan; D000077157:Sorafenib