| The term Janus was originally traced back to the double-faced gods revered by the ancient Romans.After being introduced into the scientific community,researchers classified a class of particles with special anisotropic properties as Janus particles.Compared with isotropic nanoparticles,the special structure or anisotropic chemical composition of Janus nanoparticles makes it have the advantages of multifunctional integration,showing great potential,and injecting fresh vitality into various fields.Especially in the emerging field of nanomedicine,the multi-functional integration of Janus nanoparticles can further enhance the anti-tumor effect of single-function nanoparticles to obtain better therapeutic effects.The anti-tumor effect of the existing single-function nanomedicine is not ideal and has certain limitations.Therefore,it is urgently needed to develop a nanomedicine with multiple functions to improve its therapeutic effect.Based on the weak acid environment of the tumor and the specific molecules on the surface of the tumor cells,the pH-sensitive charge reversal function and targeting function can enhance the uptake of tumor cells.The Janus particles can integrate the two functions,and their synergistic effect is expected to give nanomedicines more efficient tumor killing capabilities.Based on this,this paper proposed a strategy that focuses multiple characteristics on a single carrier to achieve synergy.First,the mesoporous silica nanoparticle(MSN)was prepared by the template method,and the tumor targeting ligand(HA)and charge inversion group(DMMA)were modified on its two hemispheres,respectively.After DOX was loaded into the nanocarriers,the bifunctional Janus nanoparticles(HA-JMSN/DOX-DMMA)were finally constructed.This paper demonstrated the successful synthesis of the Janus nanodrug by visual analysis of scanning electron microscope and transmission electron microscope,and evaluation of particle size and zeta potential distribution,FTIR spectrum,UV-vis spectrum,and fluorescence spectrum.In addition,the DOX release and the surface zeta potential of HA-JMSN/DOX-DMMA were measured under different pH environments,which proved that it had a weak acid-responsive drug release ability and charge reversal function.In addition,the paper evaluated Janus nanoparticles at the cellular level.The hemolysis experiment based on the interaction of HA-JMSN-DMMA and red blood cells showed a hemolysis rate of less than 1% at a high concentration of 500 ?g/mL,indicating that the Janus nanoparticles had excellent biocompatibility.And the cytological evaluation was performed on this subject using A549 cells as a model,the results of which showed that HA-JMSN/DOX-DMMA had better cytotoxicity and cell uptake than isotropic nanoparticles.Secondly,the results of the endocytosis pathway showed that the endocytosis of HA-JMSN/DOX-DMMA involves both clathrin-mediated endocytosis and micropinocytosis,further confirming that HA and DMMA modified on the two hemispheres of the nanodrug were involved in the interaction between the nanoparticles and tumor cells.Finally,this paper conducted an in vivo HA-JMSN/DOX-DMMA biodistribution and anti-tumor treatment evaluation,which showed much higher drug aggregation in the tumor site than the free DOX group,18.67% tumor growth inhibition rate and 70% survival rate.This result proved that the nanodrug could effectively reduce the side effects of DOX while achieving tumor targeting,and could obtain a significant tumor growth inhibition effect and improve the survival rate of tumor-bearing mice.In addition,the Janus nanodrug exhibited a tumor treatment effect superior to isotropic nanomedicine.The above results showed that HA-JMSN/DOX-DMMA could combine active targeting and charge reversal function for synergistic effect,and delivered drugs into tumors to achieve effective killing effect.It is a nanodrug with great potential application value. |
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