The Study On Anti-tumor Activities And Targeting Of HCPT/CTS-TPP-FA

HCPT is an anticancer drug.It is commonly used in clinical.Sodium salt of HCPT frequently used in the country.It has rapid metabolism and short half-life.In addition,sodium salt of HCPT is instability.It met the light will break down,can decrease the efficacy and increased adverse reactions.In order to solve the short biological half-life and the drug instability of Sodium salt of HCPT,so this experiment use nano-particles which was made of HCPT that was wraped by chitosan which coupling folic acid and sodium polyphosphate,to avhive the cancer targeting therapy and delayed release;improve the bioavailability;reduce the dosage of administration and toxic and side effect.The experiment used MTT assay anti-tumor effects in vitro.Using MTT assay to observe the effect of HCPT/CTS-TPP-FA and HCPT/CTS-TPP on proliferation of human liver cancer cell line HepG-2,human lung cancer cell line A549,human breast cancer cell line MCF-7 and human umbilical vein endothelial cells ECV304.The S180 sarcoma was inoculated in armpit of mice,observed antitumor activity of HCPT/CTS-TPP-FA group in vivo studies.In the study of nanoparticles targeting,we determined organization concertration of HCPT/CTS-TPP-FA with HPLC,to compare the distribution of HCPT/CTS-TPP-FA and HCPT/CTS-TPP in the heart,liver,spleen,lungs,kidney and serum of the mouse.Above experimental results show that both nanoparticles inhibit the proliferation of these cells,and both were not significantly different(P>0.05).In vivo anti-tumor effect study showed inhibition rate of HCPT group,HCPT/CTS-TPP-FA group and HCPT/CTS-TPP-FA group was respectively 52.91%,40.06%and 70.82%respectively.Targeted studies showed that Te,Re and Ce values of both nanoparticles in mice liver,spleen,lung,kidney are greater than 1,and therefore this experiment nanoparticles targeted to the liver,spleen,lung,and kidney.From the above results HCPT/CTS-TPP-FA has a cytotoxic effect on human liver cancer cell line HepG-2,human lung cancer cell line A549,human breast cancer cell line MCF-7 and human umbilical vein endothelial cells ECV304,and there was no significant difference from HCPT.In vivo anti-tumor effect study that HCPT/CTS-TPP-FA can inhibit tumor growth of S180 tumor-bearing mice.HCPT/CTS-TPP-FA targeted to the liver,spleen,lung,kidney,so that the anti-tumor effect of HCPT is wider range.