DongMei Yu1, Wei Li2, Yueying Zhang3, Bin Zhang4. 1. Department of Public Health, Shandong Jining No. 1 People's Hospital, Jining, 272011, Shandong, PR China. 2. Department of Science Research, Shandong Jining No. 1 People's Hospital, Jining, 272011, Shandong, PR China. 3. Department of Experimental Pathology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, 250062, Shandong, PR China. 4. Department of Oncology, Shandong Jining No. 1 People's Hospital, Jining, 272011, Shandong, PR China. Electronic address: hangbjnph@163.com.
Abstract
CONTEXT: Combination of chemotherapy and nucleic acid therapy generally take advantage of drugs anti-tumor activity together with DNA capacity to transfect cancer cells, showing great promise in cancer treatment. However, effective co-delivery of drugs and DNA in a single carrier for cancer treatment remains a challenge. OBJECTIVE: This study aimed to design a tumor targeted, pH sensitive nanocarriers for the co-delivery of gene and drug. MATERIALS AND METHODS: Hyaluronic acid - acid sensitive linker - 1,2-distearoyl phosphatideylethanolamine copolymers (HA-as-DSPE) were synthesized. HA-as-DSPE modified, paclitaxel and pDNA loaded solid lipid nanoparticles (HA-PTX/pDNA SLN) was prepared. The physicochemical properties like morphology, size, and zeta potential as well as release properties were evaluated. The ability and therapeutic effects of the novel system for the co-delivery of PTX and pDNA were demonstrated in vitro and in vivo. RESULTS: In vitro experiments and in vivo animal studies both confirmed that the HA-PTX/pDNA SLN system could promote the inhibition of tumor, at the same time deliver and transfect gene into the cancer cells. DISCUSSION AND CONCLUSION: Highest efficiency achieved by HA-PTX/pDNA SLN might result from the HA ligands that targeted the receptors on the cancer cells, the enhanced cellular uptake by the SLN formulations and also the pH sensitive bound of the carriers let the drug release more in the tumor cells. It could be concluded that HA-PTX/pDNA SLN could be used as a promising delivery system for drug and gene combination therapy.
CONTEXT: Combination of chemotherapy and nucleic acid therapy generally take advantage of drugs anti-tumor activity together with DNA capacity to transfect cancer cells, showing great promise in cancer treatment. However, effective co-delivery of drugs and DNA in a single carrier for cancer treatment remains a challenge. OBJECTIVE: This study aimed to design a tumor targeted, pH sensitive nanocarriers for the co-delivery of gene and drug. MATERIALS AND METHODS:Hyaluronic acid - acid sensitive linker - 1,2-distearoyl phosphatideylethanolamine copolymers (HA-as-DSPE) were synthesized. HA-as-DSPE modified, paclitaxel and pDNA loaded solid lipid nanoparticles (HA-PTX/pDNA SLN) was prepared. The physicochemical properties like morphology, size, and zeta potential as well as release properties were evaluated. The ability and therapeutic effects of the novel system for the co-delivery of PTX and pDNA were demonstrated in vitro and in vivo. RESULTS: In vitro experiments and in vivo animal studies both confirmed that the HA-PTX/pDNA SLN system could promote the inhibition of tumor, at the same time deliver and transfect gene into the cancer cells. DISCUSSION AND CONCLUSION: Highest efficiency achieved by HA-PTX/pDNA SLN might result from the HA ligands that targeted the receptors on the cancer cells, the enhanced cellular uptake by the SLN formulations and also the pH sensitive bound of the carriers let the drug release more in the tumor cells. It could be concluded that HA-PTX/pDNA SLN could be used as a promising delivery system for drug and gene combination therapy.