Study On Tumor Membrane Vesicles With Penetration And Photodynamic Therapy Potential

At present,the anti-tumor nano-drug delivery system is mainly composed of organic or inorganic nanoparticles,which is of great help to improve the efficacy of anti-tumor chemotherapy and reduce side effects.However,the biocompatibility of synthetic nanomaterials has always been a problem.Therefore,nanovesicles made from natural cell membrane have attracted more and more researchers’attention.Tumor cell membrane vesicles have good biocompatibility and targeting ability,which are suitable for drug delivery systems.Vesicles prepared from the cell membrane can interact with tumor cells,and help to deliver drugs to tumor cells.At the same time,due to the deformation of cell membrane vesicles,it can help anti-tumor drugs penetrate into deep tumor to achieve better anti-tumor effect.Photodynamic therapy(PDT)is a non-invasive therapy for local tumor treatment,with advantages like low toxicity and broad effectiveness for a wide range of tumors.The hydrophobicity of most photosensitizers make it possible to combine photosensitizers with nanovesicles made from tumor cell membranes to construct a new kind of tumor penetrating nano-carriers to gain a better PDT effect.In this paper,the macromolecule(PGP)with amphiphilic structure were synthesized and characterized by nuclear magnetic resonance(~1H-NMR)and fourier transform infrared spectroscopy(FT-IR).Subsequently,the co-incubation experiment of PGP and cells verified that PGP could be incorporated into the cell membrane through hydrophilic and hydrophobic action.Due to the hydrophilic and hydrophobic interaction between PGP and cell membrane,membrane modified by PGP can be obtained through the self-assembly of PGP and cell membrane,and then nanometer membrane vesicles PGPM can be obtained through membrane extrusion.The morphology and size of vesicles were characterized by TEM and DLS.The prepared vesicles have a micellar hollow structure with a particle size of about 220 nm.Flow cytometry was used to investigate the presence of photosensitizer on PGPM vesicles.It was found that porphyrin fluorescence signal was present on the prepared vesicles,with a positive rate of over 70%,indicating the successful preparation of PGPM vesicles.Finally,the cytotoxicity of the prepared amphiphilic molecules PGP and PGPM vesicles was investigated.The biocompatibility of PGP molecules and PGPM vesicles under non-light conditions was good,indicating that the PGP molecules could be used as drug delivery systems.In vitro cytotoxicity experiments showed that both PGP molecules and PGPM vesicles could inhibit the proliferation of 4T1 cells by PDT under the irradiation of 635 nm laser,and the tumor cell spheroid model was further adopted to verify the penetration of the PGPM vesicles.These results suggest that PGPM may be an effective treatment for cancer.