Stacking of doxorubicin on folic acid-targeted multiwalled carbon nanotubes for in vivo chemotherapy of tumors

Drug Delivery

Yong Hu¹  Xiangyang Shi¹  Yan Yan²  Shimeng Yin³  Tian Song³  Ruizhi Wang³  Rongyue Sun³ 

[1] College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, P. R. Chin;Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, P. R. China;Department of Radiology, Huadong Hospital, Fudan University, Shanghai, P. R. China;

关键词: Multiwalled carbon nanotubes;    polyethyleneimine;    doxorubicin;    folic acid;    tumor targeting;   

DOI  :  10.1080/10717544.2018.1501120

来源: publisher

【 摘 要 】

In this work, we developed a novel active targeting and pH-responsive system for delivering the drug doxorubicin (DOX) to tumor sites using folic acid (FA)-modified multiwalled carbon nanotubes (MWCNTs). Acid-treated MWCNTs with carboxyl groups were first covalently conjugated with polyethyleneimine (PEI). Subsequent sequential modification with FA (via a polyethylene glycol spacer), fluorescein isothiocyanate (FI), and acetic anhydride/triethylamine resulted in multifunctional FA-bound MWCNT (MWCNT-PEI.Ac-FI-PEG-FA) nanomaterials that possessed exceptional colloidal stability and good biocompatibility in a given concentration range. The FA-bound MWCNTs were characterized using various techniques and exhibited a high drug loading and an encapsulation efficiency as high as 70.4%. DOX/MWCNT-PEI.Ac-FI-PEG-FA nanocomplexes (DOX/MWCNT NCs) exhibited pH-responsive release in acidic environments. Importantly, the DOX/MWCNT NCs targeted tumor cells overexpressing FA receptors (FARs) and effectively inhibited their growth. In vivo anticancer experiments demonstrated that DOX/MWCNT NCs not only enhanced the suppression of tumor growth but also decreased the side effects of free DOX. The developed FA-modified MWCNTs with an unconventionally high DOX loading boosted in vivo anti-tumor efficacy, and the lower systemic toxicity may be utilized for tumor therapy upon clinical translation.

【 授权许可】

CC BY