Combination strategy using engineered nanoparticles to enhance therapeutic treatment

Chemotherapy is one of most common cancer treatments in clinics. In most cases, clinical responses show that the efficacy of chemotherapy is limited by the development of multidrug resistance (MDR) in cancer cells during a long period of treatment. To overcome the MDR in cancer treatment, a combination strategy to enhance chemotherapy treatment efficacy has been developed. In this research, we have employed layered double hydroxide nanoparticles to co-deliver siRNA and anticancer drugs (such as Fluorouracil and Methotrexate) to treat the various cancer cells (MCF-7, U2OS and HCT116). Our studies have demonstrated that LDHs are an efficient carrier to deliver anionic anticancer drugs such as MTX and 5-FU to inhibit the breast cancer cell MCF-7, colon cancer cell HCT116 and osteocarcinoma cancer cell U2OS. Nevertheless, co-delivery of siRNA and 5-FU delivered by LDH NPs has significantly inhibited the cancer cell growth.

In vitro cell tests have demonstrated that treatment with siRNA-5-FU/LDH nanocomplexes caused ~70% cell death, while treatment with either 5-FU/LDH or siRNA/LDH at the same concentration resulted in only 46% or 34% cell death. These data clearly show that a combination treatment with siRNA and 5-FU with LDH nanoparticles significantly suppresses MCF-7 cell growth, probably a result of the synergistic effect of two therapeutics on cancer cells by effectively inducing cell death in complementary pathways.

In addition, we found that the cell death of cancer treated by combination strategy is caused by mitochondrial apoptotic pathway.

Co-delivery of siRNAs and anticancer drugs by LDHs has great potential as a novel approach for effective cancer treatment. This work has been published in Biomaterials by Dr Li Li and Professor Zhi Ping (Gordon) Xu.