Co-delivery of dual chemo-drugs with precisely controlled, high drug loading polymeric micelles for synergistic anti-cancer therapy

2020 ◽  
Vol 8 (3) ◽  
pp. 949-959 ◽  
Author(s):  
Yuchen Wu ◽  
Shixian Lv ◽  
Yongjuan Li ◽  
Hua He ◽  
Yong Ji ◽  
...  

The introduction of donor-receptor coordination between micelles and drug payloads provides a precise co-delivery strategy for two different chemo-drugs with high drug loading and ROS responsiveness.

2013 ◽  
Vol 42 (24) ◽  
pp. 8918 ◽  
Author(s):  
Baixiang Wang ◽  
Weiyan Meng ◽  
Ming Bi ◽  
Yuxin Ni ◽  
Qing Cai ◽  
...  

2018 ◽  
Vol 166 ◽  
pp. 235-244 ◽  
Author(s):  
Shuo Fang ◽  
Yongpeng Hou ◽  
Longbing Ling ◽  
Danquan Wang ◽  
Muhammad Ismail ◽  
...  

2020 ◽  
Vol 6 (45) ◽  
pp. eabc1725
Author(s):  
Yinxian Yang ◽  
Bingjun Sun ◽  
Shiyi Zuo ◽  
Ximu Li ◽  
Shuang Zhou ◽  
...  

Rational design of nanoparticulate drug delivery systems (nano-DDS) for efficient cancer therapy is still a challenge, restricted by poor drug loading, poor stability, and poor tumor selectivity. Here, we report that simple insertion of a trisulfide bond can turn doxorubicin homodimeric prodrugs into self-assembled nanoparticles with three benefits: high drug loading (67.24%, w/w), high self-assembly stability, and high tumor selectivity. Compared with disulfide and thioether bonds, the trisulfide bond effectively promotes the self-assembly ability of doxorubicin homodimeric prodrugs, thereby improving the colloidal stability and in vivo fate of prodrug nanoassemblies. The trisulfide bond also shows higher glutathione sensitivity compared to the conventional disulfide bond, and this sensitivity enables efficient tumor-specific drug release. Therefore, trisulfide bond–bridged prodrug nanoassemblies exhibit high selective cytotoxicity on tumor cells compared with normal cells, notably reducing the systemic toxicity of doxorubicin. Our findings provide new insights into the design of advanced redox-sensitive nano-DDS for cancer therapy.


Author(s):  
Xiangdong Xue ◽  
Marina Ricci ◽  
Haijing Qu ◽  
Aaron Lindstrom ◽  
Dalin Zhang ◽  
...  

2020 ◽  
Vol 7 (4) ◽  
pp. 359-369
Author(s):  
Hai Zhang ◽  
Jianqin Yan ◽  
Heng Mei ◽  
Shengsheng Cai ◽  
Sai Li ◽  
...  

Abstract Challenges associated with low-drug-loading capacity, lack of active targeting of tumor cells and unspecific drug release of nanocarriers synchronously plague the success of cancer therapy. Herein, we constructed active-targeting, redox-activated polymeric micelles (HPGssML) self-assembled aptamer-decorated, amphiphilic biodegradable poly (benzyl malolactonate-co-ε-caprolactone) copolymer with disulfide linkage and π-conjugated moieties. HPGssML with a homogenous spherical shape and nanosized diameter (∼150 nm) formed a low critical micellar concentration (10−3 mg/mL), suggesting good stability of polymeric micelles. The anticancer drug, doxorubicin (DOX), can be efficiently loaded into the core of micelles with high-drug-loading content via strong π–π interaction, which was verified by a decrease in fluorescence intensity and redshift in UV adsorption of DOX in micelles. The redox sensitivity of polymeric micelles was confirmed by size change and in vitro drug release in a reducing environment. Confocal microscopy and flow cytometry assay demonstrated that conjugating aptamers could enhance specific uptake of HPGssML by cancer cells. An in vitro cytotoxicity study showed that the half-maximal inhibitory concentration (IC50) of DOX-loaded HPGssML was two times lower than that of the control group, demonstrating improved antitumor efficacy. Therefore, the multifunctional biodegradable polymeric micelles can be exploited as a desirable drug carrier for effective cancer treatment.


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