Preparation And Properties Of Redox And Light Dual-responsive Polymer Nanomicelles

In recent years,nanodrug carriers for antitumor drug delivery have been widely studied,and researchers have designed various stimulus-responsive nanodrug carriers based on the differences between the microenvironment of tumor cells and normal cells.These nanodrug carriers can produce corresponding changes in chemical properties or physical structures under the stimulation of internal and external environments,leading to the depolymerization of drug-carrying micelles and accelerated drug release,thus achieving controlled drug release effects.Single responsive nanodrug carriers have been widely reported.In this paper,we designed polymeric nanomicelles with dual redox and light responsiveness from internal stimuli of cellular microenvironment combined with external stimuli of light response,and the study is as follows.(1)mPEG-SS-TOS,a polymeric drug-carrying material with redox responsiveness,was synthesized by bridging hydrophobic D-?-tocopheryl succinate(TOS)and hydrophilic poly(ethylene glycol)monomethyl ether(m PEG)through an amidation reaction using cystamine with disulfide bonds.The structure of m PEG-SS-TOS was determined by nuclear magnetic hydrogen spectroscopy and infrared spectroscopy;the prepared m PEG-SS-TOS nanomicelles were prepared with a critical micelle concentration of 7.9 mg/L,an average particle size of62.08 nm,a PDI of 0.1478,and a zeta potential of-3.5 m V.Transmission electron micrographs showed that the micelles were uniformly distributed,homogeneous in size,and spherical in structure;the disulfide bonds in the nanomicelles were broken after DTT treatment leading to the disruption of the nanomicelle structure.It was confirmed that the m PEG-SS-TOS nanomicelles had certain reduction responsiveness;the m PEG-SS-TOS nanomicelles loaded with DTX,with an average particle size of 72.25 nm,PDI of 0.1562 and zeta potential of 0.95m V,had good stability and dispersion,and the encapsulation rate and drug loading capacity were 89.62%and 8.56%,respectively,after After DTT treatment,the cumulative release rate of DTX reached 91.56%within 24 h.It possesses redox-responsive drug release behavior and can be used as an intelligent delivery vehicle for drugs.(2)Demagnetized chlorophyllic acid A(Pheo A)was extracted from Chinese silkworm sand as a photosensitive drug,and its structure was determined by nuclear magnetic hydrogen spectroscopy and infrared spectroscopy,and the water solubility of Pheo A was improved by modification of demagnetized chlorophyllic acid A with vitamin E polyethylene glycol succinate(TPGS),and the structure of TPGS-Pheo A was determined by nuclear magnetic hydrogen spectroscopy and infrared spectroscopy,and the measured Pheo A with 85.23%affinity on TPGS;synthesized materials(P₁₂₃-S-SS-TOS)with dual redox and light responsiveness by reacting polyether P₁₂₃,thiohydroxyacetic anhydride,D-?-tocopheryl succinate and cystamine in dichloromethane system by esterification and amidation reactions,and determined the structures of their intermediate and final products by NMR hydrogen spectroscopy and infrared spectroscopy.The prepared TPGS-Pheo A/P₁₂₃-S-SS-TOS nanomicelles had a critical micelle concentration of 6.3 mg/L,an average particle size of 33.6±2.28 nm,a PDI of 0.198±0.03,and a zeta potential of-9.7±1.3 m V.The transmission electron micrographs showed that the nanomicelles had a spherical structure,which was basically the same as the results of the particle size measurement.TPGS-Pheo A/P₁₂₃-S-SS-TOS nanomicelles have a certain p H stability,and have high stability with low adsorption of proteins and no aggregation and sedimentation;low concentration of DTT has little effect on the micelles,while high concentration of DTT can completely cleave the nanomicelle structure into lamellar structure and aggregation,which confirms that the nanomicelles have certain redox sensitivity to DTT.The redox sensitivity of the nanomicelles to DTT was confirmed.The oxidative destruction of the thioether bonds by the ROS generated from the nanomicelles under670 nm red light irradiation caused the transformation of the thioether bonds from hydrophobic to hydrophilic,resulting in the destruction of the micelle structure to a certain extent,which confirmed the photoresponsiveness of the nanomicelles.(3)The DOX-loaded TPGS-Pheo A/P₁₂₃-S-SS-TOS nanomicelles were prepared with an average particle size of 45.49±2.58 nm,a PDI of 0.26±0.08,and a zeta potential of-3.62±0.9m V,which had good stability and dispersion,and the transmission electron micrographs showed that the nanomicelles were spherical in structure and uniformly dispersed.The encapsulation rate and drug loading of the nanomicelles were 87.15%and 3.35%,respectively.The ROS yield of the nanomicelles under 670 nm red light excitation was 0.52.The drug release study showed that the disulfide bonds inside the micelles were severed and the thioether bonds were oxidized under the simultaneous application of DTT treatment and 670 nm red light irradiation,resulting in a cumulative DOX release rate of 95%with both redox and light responsive release behaviors.