Targeting The Anti-choriocarcinoma Effect Of Prodigalin Chitosan Quaternary Ammonium Salt Nanoparticles

Chitosan derivatives is by modification of natural cationic polysaccharide chitosan.It not only inherits the chitosan characteristics of safe non-toxic,can be degradationed by variety enzyme in a organisms.But also have a good water solubility,even can be dissolved in water and oil,provides a prerequisite for drug delivery carriers.Prodigiosin is one of the new anticancer drugs.It has anti-bacteria,anti-fungal,anti-malaria,anti-tumor immunosuppressive activity and other biological activities.In vitro studies have shown that prodigiosin can inhibit different cancer cells proliferation and induce apotosis in various cancer cells,the side effect on normal cells is very small.toxicity to normal cells is very small.Peptide VAR2CSA can specifically combined with the chondroitin sulfate A?CSA?on the surface of placental trophoblast cells,also can bind to the surface of cancer cells.So,peptide VAR2CSA can be developed as"the guider"for the cancer treatment.This paper synthesized the three kinds of chitosan derivatives that have good water soluble:N-2-hydroxypropyl Trimethyl Ammonium Chloride Chitosan?N-2-HACC?,polypeptide VAR2CSA-N-2-hydroxypropyl Trimethyl Ammonium Chloride Chitosan?CSA-N-2-HACC?,Scrambled polypeptide-N-2-hydroxypropyl trimethylammonium chloride ammonium Chitosan?SCR-N-2-HACC?.And,strain HDZK-BYSB107 prodigiosin for a model drug,the polyelectrolyte.By ¹H NMR and in vitro cell uptake tests showed that the polypeptide VAR2CSA was successfully grafted onto the N-2-HACC and maintained a good activity.At the same time,the physical and chemical characteristics,safety,and in vitro release characteristics of nanoparticles were evaluated.Test results show that:1?The chitosan derivatives of N-2-HACC,SCR-N-2-HACC and CSA-N-2-HACC were synthesized successfully.And the result of cytotoxicity assay shows that,N-2-HACC,SCR-N-2-HACC and CSA-N-2-HACC were similar to chitosan,whith is safe and nontoxic.2?Successful purification and identification of the strains HDZK-BYSB107prodigiosin.And the result of cytotoxicity assay show that,the PG has strong killing effect on choriocarcinoma cell lines?JEG₃?.The side effects of human renal epithelial cell line?293T?were very small,and no obvious growth inhibited was found;3?The results of ¹H NMR and in vitro cell test show that the polypeptide VAR2CSA can be"grafted"to N-2-HACC,and maintained a good activity,and can be targeted to JEG3 cells;4?The optimum conditions of preparation of PG/CSA-N-2-HACC/CMC-NPs to determined,the CSA-N-2-HACC concentration is 1.20mg/mL,CMC concentration is0.6 mg/mL,strains HDZK-BYSB107 prodigiosin concentration is 0.6mg/mL.5?In vitro release test results show that the nanoparticles were prepared with obvious slow release characteristics.And,the strains HDZK-BYSB107 prodigiosin release amount was higher in the pH=5.3.This characteristic can be very good in blood circulation;6?Storage stability test results show that the external shape,particle size are not significantly changed to avoid light placement for three months in 4?,-20?;7?The result of in vivo treatment effect test show that PG/CSA-N-2-HACC/CMC-NPs treatment has the best effect and whit no side effects,compared with the other treatment groups.It proved that the polypeptide VAR2CSA can be combined with the choriocarcinoma?JEG₃?cells specificity and provides a way for cancer therapy.This study constructed using chitosan derivatives as the carrier,strain HDZK-BYSB107 prodigiosin was used as model of drug delivery system,to preserve the integrity of the polypeptide VAR2CSA.To achieve the nanoparticles in vivo for long time,and to achieve the goal of safety,efficient,rapid,low side effect.At the same time,it also provides the theoretical basis for the clinical application of the strain HDZK-BYSB107.