Combination therapy using Smac peptide and doxorubicin-encapsulated MUC 1-targeted polymeric nanoparticles to sensitize cancer cells to chemotherapy: An in vitro and in vivo study.

International Journal of Pharmaceutics
Mojgan NejabatMohammad Ramezani

Abstract

Targeting inhibitors of apoptosis proteins (IAPs) family comprising high level expression in many cancer cells, could sensitize tumor cells to conventional chemotherapies. In the present study, we designed both doxorubicin and SmacN6 (an antagonist of the IAPs) encapsulated polymeric nanoparticles (NPs) and investigated their synergistic effect of combination therapy in vitro and in vivo. According to the results, NPs-SmacN6 significantly enhanced the cytotoxicity effect of NPs-DOX and reduced its IC50 in MCF-7, 4T1 and C26 cancer cells. Western blot analysis confirmed mechanism of cell apoptosis via caspase activation through intrinsic and also extrinsic pathways. Moreover, 5TR1 aptamer-modified NPs could effectively deliver DOXor SmacN6 to C26 cancer cells (MUC1 positive) in comparison with the non-targeted one (p < 0.001). However, they could not be efficiently internalized into CHO cells (MUC1 negative), showing less cytotoxicity in this cell line. In vivo experiments in BALB/c mice bearing C26 tumor indicated that Apt-NPs-DOX in combination with Apt-NPs-SmacN6 had significant tumor growth inhibition in comparison with mice receiving either free DOX or Apt-NPs-DOX with p < 0.0001 and p < 0.05, respectively. Our results reve...Continue Reading

Related Concepts

Related Feeds

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis