Abstract

Combination therapy, as a treatment modality with simultaneous use of two or more therapeutic agents, could provide more attention in the field of cancer therapy. In this regard, the combination of anti-cancer agents could increase the drug efficacy due to reduction of tumor growth and metastasis as well as apoptosis induction while reducing the drug resistance. In the current study, a single-walled carbon nanotube (SWCNT) nanoparticulate carrier, modified with polyethylene glycol and branched polyethylenimine (PEI 10 kDa), was synthesized for the simultaneous delivery of plasmid encoding survivin (psur) shRNA and SN38. The aforementioned nanoparticle was tagged with a targeting peptide, PNC27, for enhancing the internalization of therapeutic agents to cancerous cells. Competition assay using flow cytometry (FCM) experiment revealed the higher uptake of the targeted platform into C26 cells, treated with targeted carrier whereas cells treated with either untargeted NP or pre-treated with an excess amount of free PNC27 peptide exhibited lower internalization efficiency. Furthermore, compared with either irinotecan at high dose or SWCNT-PEG10PEI(10Br)/SN38/pEGFP at an equivalent dose, SWCNT-PEG10PEI (10Br)/SN38/psur shRNA and SWCNT-PEGI 0PEI OBO/SN38/psur shRNA/PNC27 significantly reduced the tumor volume in C26 tumorized female BALB/c mice, demonstrating the synergistic effects of SN38 and psur shRNA. In addition, the carrier conjugated with PNC27 facilitated the accumulation of psur shRNA and SN38 in cancer tissue causing a substantial inhibitory effect compared to that of untargeted groups. It could be concluded that the novel modified SWCNT loaded with SN38 and psur shRNA could enhance the therapeutic efficacy in vitro and in vivo, thereby providing an innovative approach for cancer treatment.