Novel targeted delivery of Lipid-Platinum-Chloride nanoparticles combined with photodynamic therapy applied in pancreatic cancer

• Main Authors: Jia-Haur Chen, 陳家豪
• Other Authors: Yih-Chin Hsu,Ph.D.
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/49966963276492667844

碩士 === 中原大學 === 生物科技研究所 === 105 === Cisplatin (CDDP) has been commonly used as a chemotherapeutic drug and limited due to high toxicity as well as the side effects. The CDDP has poor solubility in water and to take advantage of this a new method was performed in this study to load CDDP in nanoparticles via reverse microemulsion technique and termed as Lipid-Pt-Cl nanoparticles (LPC NPs). LPC NPs were enhance with anisamide to target over-expressing sigma receptor tumor cells. Western blot analysis confirmed that sigma receptor were highly expressed by PANC-1 and MIAPaCa-2 cells. The particle size measured was 21.6 ± 1.5 nm with zeta potential of 31.0 ± 1.1 mV and the drug loading capacity of 71.0 ± 10.3% wt. In vitro study in PANC-1 & MIAPaCa-2 cells showed that the cell viability decreased with CDDP encapsulated in LPC NPs which has a lower dosage as compared with free CDDP. This result indicating LPC NPs exhibit the anticancer efficacy of cisplatin to a lower dose than using free CDDP alone. In vivo study, we used BALB/c Nude mice to create animal model distributed as 5 groups (n=5) such as: PBS, CDDP, LPC, PDT+CDDP and PDT+LPC at a dose of 3mg Pt/kg for CDDP and LPC. The photosensitizer used was photosan at a dose of 2mg/kg for photodynamic therapy (PDT). All of the treatments observed for 23 days. The results showed LPC can inhibit tumor growth for both of cell lines. PANC-1 tumor growth rate compared with control PBS group: PDT+LPC group decrease 71.5 % (p<0.01), LPC group decrease 63 % (p<0.01), PDT+CDDP group decrease 45 % (p<0.01), CDDP group decrease 30.8 % (p<0.01); MIAPaCa-2 tumor growth rate compared with control PBS group: PDT+LPC group decrease 71.3 % (p<0.01), LPC group decrease 54.2 % (p<0.01), PDT+CDDP group decrease 45.5 % (p<0.01), CDDP group decrease 16.5 % (p<0.01). Despite inhibit the tumor growth with LPC alone, when it combined with PDT a better result found as the tumor size significantly decreased. In addition, the LPC alone need injected 3 times (0, 7, 14 days), but combined treatment just one times. All results were analysed with Sigma Plot software with significant value (p<0.01).Therefore, LPC have a potential as enhancing anticancer drug for chemotherapy. Because it’s small size, high drug loading and was enhanced with target ligand of anisamide. Importantly in combination with PDT the therapeutic effect have shown to be more effective in treating pancreatic cancer, PANC-1 and MIAPaCa-2 cells.