Construction And Applications Of Mesoporous Silica And Molybdenum Disulfide Based Multifunctional Nano-theranostic Agent

Cancer,as one of the most intractable clinical diseases,has become the biggest threat to human survival.Nevertheless,the booming nanomedicine has brought a new dawn for cancer treatment.Using nanoparticles to prepare a reasonable drug delivery system has become the research hot in nanomedicine.More importantly,in order to meet the higher standards of precision medicine,introducing imaging functions that can monitor tumor treatment in real time reasonably and targeting ligands that actively target tumor cells has become promising when constructing the drug delivery system.Mesoporous silica nanoparticles?MSN?have unique advantages in the construction of drug delivery carriers due to their excellent biocompatibility,large specific surface area and pore size and easy modification.Based on these,we first propose to use biodegradable MSN?bMSN?as nanocarriers to construct a multifunctional nano-theranostic agent for imaging diagnosis of cancer and targeted delivery of antitumor drugs.At the same time,photothermal therapy,which has the advantages of good safety and fewer invasion,has also become one of the most emerging methods for cancer treatment.Therefore,the combination of photothermal agents and chemotherapy drugs will realize photothermal-chemotherapy bimodal treatment,which can better solve the problem of insufficient effect of simple chemotherapy.Molybdenum disulfide?MoS₂?as a photothermal agent was widely studied in recent years.It has great potential in constructing a photothermal-chemotherapy bimodal treatment system due to its good photothermal performance and better photoacoustic?PA?imaging effect.Therefore,based on the above experimental ideas,the research work of this paper is carried out from the following two aspects:?1?Based on the good properties of bMSN,the BSA-Gd/Au prepared by biomimetic mineralization was modified on the surface to endow the nanocarrier with magnetic resonance?MR?imaging and near infrared fluorescence?NIFR?imaging functions.Subsequently,folic acid?FA?that could actively target various tumor cells was coupled on the nanocarrier to increase the uptake of nano-theranostic agent to KB tumor cells.The successful preparation of bMSN-ss-GABA was proved by a series of characterization,the result of in vitro degradation tests showed that bMSN had the best degradation effect in the acidic environment which simulates tumor.Furthermore,bMSN-ss-GABA also has good biocompatibility,the drug transport system mediated by FA receptor can better promote the DOX uptake to the KB cells.In addition,good MR imaging and NIRF imaging of bMSN-ss-GABA can provide better imaging guidance for tumor treatment.After verifying that bMSN-ss-GABA has no obvious in vivo toxicity,the drug-loaded particles show excellent drug targeting transport function and chemotherapy effect in combination with chemotherapy drugs.Therefore,the preparation of bMSN-ss-GABA was expected to accelerate the pace of cancer diagnosis and treatment.?2?MoS₂ nanoparticle with good photothermal effect and PA imaging effect was used as the core,and polydopamine?PDA?was coated on the surface of it.Then,the metal-organic framework?MOF?with high drug loading was prepared by the coordination of hydroxyl and carboxyl groups with Fe ions.After loading the antitumor drug DOX into the MOF shell,hyaluronic acid?HA?was modified to the surface of the drug-loaded particles to achieve specific targeting transport of DOX to 4T1 tumor cells.The successful construction of drug carrier?MoS₂-PMA?and its good photothermal effect and light stability are proved by various characterization.The MR imaging combined with PA imaging can enhance the sensitivity of tumor diagnosis.At the same time,the results of in vivo and in vitro experiments showed that the uptake of drug-loaded particles by 4T1 tumor cells increased significantly after modifying HA.Most importantly,the combined photothermal-chemotherapy treatment has the best therapeutic effect both in vivo and in vitro.Hence,the prepared DOX@MoS₂-PMA is available to use for multi-modality tumor theranostics.In summary,bMSNs was first used to construct the multifunctional and biodegradable nanocarrier for cancer theranostics.then combined MoS2 with MOF to fabricate a multi-modality theranostic nanoplatform.It is expected that above studies will promote the clinical application of biodegradable nanocarriers and the development of the multifunctional nano-theranostic agent.