Preparation And Properties Of Chemo-photothermal Synergistic Drug Delivery System Based On Cellulose Nanocrystals

Cellulose nanocrystals(CNC)are promising for applications in the field of drug delivery owing to their desirable properties,such as rod-like structure,massive surface hydroxyl groups and low cytotoxicity.In this work,CNC was grafted with polycaprolactone-b-poly(2-(dimethylamino)ethyl methacrylate)(PCL-b-PDMAEMA)to encapsulate anticancer drug doxorubicin(DOX)and photosensitizer indocyanine green(ICG)for chemo-photothermal synergistic therapy.Dissipative particle dynamics(DPD)simulations were used to study the self-assembly mechanism of the polymer brush;The study could provide theoretical guidance for the design and optimization of CNC-based drug delivery.CNC were prepared from sulfuric acid hydrolysis of microcrystalline cellulose.Then,CNC-g-PCL-b-PDMAMEA was created via ring-opening polymerization(ROP)and activators regenerated by electron transfer atom transfer radical polymerization(ARGET ATRP).Proton nuclear magnetic resonance spectra(~1H NMR)and Fourier transform infrared spectroscopy(FT-IR)analysis were used to characterize polymer structures.The results of atomic force microscopy(AFM)and differential scanning calorimetry(DSC)showed that CNC-g-PCL-b-PDMAMEA is rod-like shape with the length of 100?200 nm and the diameter of 50?70 nm and the phase transition temperature(T_m)of 50.6?.DOX and ICG were encapsulated into the polymer brush via hydrophobic interaction and electrostatic interactions to obtain drug-loaded nano-carrier system CNC-g-PCL-b-PDMAMEA@DOX/ICG.The cumulated release of DOX was only less than 40%at p H 7.4,whereas 80%at p H 5.0 within 80 h.After exerted NIR irradiation(808 nm),the DOX release rate of the nano-carrier increased significantly,which was about 5 times higher than of the group without NIR irradiation within 13 h.The nano-carrier exhibited higher cytotoxicity to Hep G2 cells under NIR irradiation than without it,indicating its chemo-photothermal synergistic antitumor effects.DPD simulations were applied to examine the effects of polymer concentration,the rod-block proportion and distribution and grafting density of side chains on the self-assembly behavior of CNC-g-PCL-b-PDMAMEA.We proposed the“rod-coil competitive mechanism”for the self-assembly of the brush polymer.The micellar structures mainly depend on the relative intensity between the orientational ordering of rod blocks and the disordered packing of the flexible blocks.The cylindrical micelles were formed when the former predominates,otherwise the spherical micelles were observed.The increasing rod-block proportion,the coil-rod-coil backbones and the asymmetric grafting side chains are beneficial to the orientation order of the polymer brush in self-assembly process,thereby inducing the formation of the cylindrical micelles.