Preparation And Properties Of Acid-Degradable Hybrid Nano-drug Carriers

Mesoporous silica（MSNs）has larger pores and higher specific surface area.The characteristics of strong drug-loading ability,strong adaptability,and easy surface modification have become the research hotspots of drug carriers in recent years.However,MSNs have a relatively stable chemical bond skeleton,which is difficult to degrade in the human body,and will accumulate in organs such as the liver,kidney,spleen,bladder,and lung,and is potentially dangerous to the human body.Hydroxyapatite（HAP）has excellent biocompatibility,non-toxicity,osteoconductivity,and physical and chemical stability,and is mainly used in bone tissue engineering and other fields.Doping a certain proportion of HAP in MSNs,changing its original stable Si-O-Si covalent bond structure,introducing Si-O-Ca²⁺ion coordination chemical bonds,thereby improving the degradation ability of MSNs in acidic environment.In this paper,p H-responsive hybrid nano-drug carriers（Mesoporous silica hybrid nanoparticles,MSHNs）were prepared by doping HAP during the synthesis of MSNs.MSHNs were loaded with doxorubicin（DOX）,and the mussel-like adhesion protein polydopamine（PDA）was coated on the surface to inhibit the free release of DOX from the mesoporous channels.The PDA coating layer also serves as a mediator layer,combined with cell membrane-like polymers and targeting ligands,to construct a drug delivery system（DDS）with both biological safety,targeting and controlled drug release capabilities.This study provides a new idea for the construction of chemotherapeutic drug carriers.This paper explores the preparation methods of MSNs and MSHNs,and conducts performance characterization and comparative analysis on them,and selects MSHNs with better degradation performance as the carrier for constructing DDS.First,MSHNs were used to load DOX in a weakly acidic environment,and PDA was modified on the surface of the DOX·MSHNs carrier to prepare a DOX·MSHNs@PDA drug delivery system.The number-average particle size of the system is 114.5 nm.After the surface is coated with PDA,the pore volume peak pore size decreases from 5.05 nm to 3.0 nm,and the drug loading rate is about 10.6%.In the PBS solution with p H=7.4,the drug release rate of the drug delivery system was only 21.2%,while in the PBS solution with p H=5.0 simulating the acidic environment of cancer cells,the drug release rate was as high as 93.1%within 96 hours.The results of this study show that DOX·MSHNs@PDA has good drug sustained release performance and acid sensitivity,which provides a basis for the subsequent construction of DDS with good performance.On the basis of DOX·MSHNs@PDA drug carrier,DOX·MSHNs@PDA@PEG was constructed by sequentially modifying the surface of dicarboxypolyethylene glycol（PEG）and coupling the cell membrane polymer PMEN targeting folic acid（FA）.The drug release study of DOX·MSHNs@PDA@PEG-PMEN/FA showed that the drug release rate of the carrier was 30.2%in PBS solution at p H=5.0 for 96 hours,compared with that of DOX·MSHNs@PDA under the same conditions The drug release rate was93.1%,a decrease of 62.9%.Exhibits good drug sustained-release ability.Cell uptake studies of MSHNs@PDA@PEG-PMEN/FA blank carrier showed that the uptake rate of MSHNs@PDA@PEG-PMEN/FA by Hela cells was very fast,and the uptake rate at 2hours and 6 hours was 2.5 times higher than that of other carriers,respectively 3.8 times,while the uptake rate of the vector by L929 cells was equivalent to other blank carriers.The cytotoxicity study of DOX·MSHNs@PDA@PEG-PMEN/FA drug delivery system and its blank carrier showed that the drug delivery system has low toxicity to L929cells,and the cell survival rate exceeds 90%;but it has a strong killing effect on Hela cells capacity,the cell viability was only 25%.It shows that the carrier has a good prospect in the treatment of cancer.