Constuction Of Biomimetic Paclitaxel Crystal Pharmaceuticals And Anti-tumor Effect On Breast Cancer

Objective: To prepare a bio-mimetic tumor cell membrane-cloaked paclitaxel nanocrystal system(NCs-BSA-CM)with good stability,biocompatibility,and antitumor activity,which consists of rod-like paclitaxel nanocrystals(NCs)as a high-dose drug core,bovine serum albumin(BSA)as a hydrophilic molecule to adjust the particle sizes of NCs-BSA and the shell of tumor cell membrane that can target tumor site.Methods:1.Preparation and characterization of NCs-BSA-CM: NCs with uniform particle size and high drug loading were prepared from free paclitaxel,followed by surface binding with BSA,and then coated with tumor cell membrane via physical extrusion.Next,the particle size,Zeta potential and stability of NCs-BSA-CM were measured by laser particle size analyzer,and the morphology of NCs-BSA-CM was characterized by transmission electron microscopy to confirm the coating of cell membrane.Meanwhile,drug loading,encapsulation efficiency and in vitro release behavior were also detected by HPLC.2.In vitro biocompatibility study of NCs-BSA-CM: The hemolysis rate of NCs-BSA-CM was studied by hemocompatibility assay and the antiproliferation activity on ECs cells was also detected by MTT to evaluate the biocompatibility of the biomimetic paclitaxel crystal pharmaceuticals.3.Evaluation of antitumor efficacy and targeting performance of NCs-BSA-CM in vitro: The cytotoxicity of NCs-BSA-CM on MCF-7 cells was investigated by MTT assay,and the apoptosis effect of NCs-BSA-CM was evaluated on MCF-7 cell utilizing the fluorescence microscopy.Subsequently,the effect of NCs-BSA-CM on the migration of MCF-7 cells was detected by scratch test,and its homologous targeting ability was measured by cellular uptake.Results: The results showed that the mean particle size of NCs-BSA was 161.62 ± 2.47 nm and the Zeta potential was-4.36 ± 0.97 m V.After coating with tumor cell membrane,the mean particle size of NCs-BSACM was 170.37 ± 2.61 nm and the Zeta potential was-13.24 ± 1.13 m V.The Encapsulation efficiency and Drug loading were 86.75 ± 3.67% and31.83 ± 4.26% respectively.In vitro stability and release study indicated that NCs-BSA-CM was stable over 7 days at room temperature,and a sustained release profile in PBS was also exhibited by NCs-BSA-CM.The study on the biocompatibility of NCs/CM showed that the hemolysis rate of NCs-BSA-CM at different concentrations was less than 2%,and the inhibition rate of NCs-BSA-CM on ECs cells was less than 30%,showing slight cytotoxicity and good biocompatibility.The antitumor activity of NCs-BSA-CM in vitro showed that NCs-BSA-CM had a significant inhibitory effect on MCF-7 cells in a dose dependent manner.And NCsBSA-CM could inhibit migration of MCF-7 cells effectively.Moreover,the cellular uptake of NCs-BSA-CM in MCF-7 cells occurred in a time dependent manner.Conclusion: Herein,we have constructed a tumor cell membranecloaked paclitaxel nanocrystal system(NCs-BSA-CM)with uniform particle size,high drug loading,good stability and biocompatibility.At cell levels,NCs-BSA-CM showed greater cellular uptake,higher cytotoxicity,which may provide new insights into and lay the groundwork for the development of new biomimetic paclitaxel nanodrug delivery system.