Co-delivery of doxorubicin and TRAIL plasmid by modified PAMAM dendrimer in colon cancer cells, in vitro and in vivo evaluation

Abstract

One strategy for cancer treatment is combination therapy using nanoparticles (NPs), which has resulted in enhanced anti-cancer effects and reduced cytotoxicity of therapeutic agents. Polyamidoamine dendrimer (PAMAM) has attracted considerable attention because of its potential applications ranging from drug delivery to molecular encapsulation and gene therapy. In this study, PAMAM G5 modified with cholesteryl chloroformate and alkyl-PEG was applied for co-delivery of doxorubicin (DOX) and plasmid encoding TRAIL into colon cancer cells, in vitro and in vivo. The results showed DOX was efficiently encapsulated in modified carrier (M-PAMAM) with loading level about 90%, and the resulting DOX-loaded M-PAMAM complexed with TRAIL plasmid showed much stronger antitumor effect than M-PAMAM containing DOX or TRAIL plasmid. On the other hand, the obtained results demonstrated that the treatment of mice bearing C26 colon carcinoma with this developed co-delivery system significantly decreased tumor growth rate. Thus, this modified PAMAM G5 can be considered as a potential carrier for co-delivery of drug and gene in cancer therapy.

Keywords:

• Combination therapy
• doxorubicin
• polyamidoamine
• cholesterol
• TRAIL plasmid

Disclosure statement

The authors declare no conflicts of interest with respect to the research, authorship, or publication of this study.

Additional information

Funding

This work was financially supported by the Mashhad University of Medical Sciences.