| Cancer has always been a huge challenge in the world of medicine.However,most anti-tumor drugs are not specific,which will inevitably cause severe damage to normal tissues during cancer treatment,traditional chemotherapy methods leading to low bioavailability and great side effects.Therefore,the smart drug delivery systems(DDS)has become a research hotspot,“smart” drug delivery systems(DDS)with a specific responsiveness to a range of stimuli,such as pH,redox conditions,temperature and light irradiation,have attracted much attention for their potential applications in drug and gene delivery.Of these stimuli,pH-responsive activation is a promising option as pH values in different tissues and cellular compartments vary tremendously.The designed dosing system has greatly increased the uptake of tumor cells and reduced the damage to normal tissues.In addition,these dosing systems may have uncontrollable drug releases,but when they enter the body,we usually do not detect its release behavior in a timely manner,so it is important to build a drug delivery system that detects the release behavior of drugs immediately.Various pH-responsive DDS,especially mesoporous silica nanoparticles(MSN)that have the high loading capacity and stability,perfect in vitro and in vivo biocompatibility and efficient surface functionalization and end-capping,have been widely investigated.To prevent premature drug release from MSN-based pH-responsive DDS,different strategies,including covalent attachment of the drug inside the mesopores or complete capping of pHresponsive polymer coatings onto MSN,have been developed.However,most of these DDS can't monitor the drug release profile in real time to avoid insufficient or excess drug dosing at the focuses.Constructing novel DDS to achieve pH-responsive drug delivery,while realize the real-time monitoring of drug release remains a challenge.The research content of this paper mainly includes the following aspects:1.Construction and preparation of UC@Si@TA-Cu composite systemFirstly,upconversion nanoparticles(UCNPs)with gadolinium as the matrix material and doped thulium and erbium were prepared by thermal decomposition method.Upconversion nanoparticals as an imaging unit of the composite system.Then,a mesoporous silicon layer(Si)was coated on the surface by the phase transfer assisted surfactant template method for drug loading.DOX was selected as the model drug in this paper,through the phenomenon of luminescent resonance energy transfer between adriamycin and UCNPs as a precondition for real-time monitoring of drug release.In order to give the drug carrier system pH sensitivity,we modified a pH-sensitive polyphenol-metal(TA-Cu)shell on its surface,the drug loading system was labeled UC@Si@TA-Cu.2.In vitro characterization of UC@Si@TA-CuIts morphology,particle size,zeta potential,fluorescence spectrum,encapsulation rate and drug loading,as well as its pH responsive release were investigated.The results showed that it had regular spherical shape,uniform particle size distribution,good up-conversion luminescence,high encapsulation rate and drug loading,and pH responsive drug release behavior.With the release of Adriamycin,the fluorescence intensity of the upconversion increased,and real-time monitoring of drug release was achieved at the solution phase level.3.The cellular level evaluation of UC@Si@TA-CuIn the cell experiment,we selected HeLa cells.Cytotoxicity of free doxorubicin,UC@Si@TA-Cu were studied by using CCK8 detection kit.The experimental results showed that the carrier materials without drug loading had good biocompatibility,and the cell lethality of drug loading materials was better than that of free doxorubicin.Cell uptake experiments showed that cells were time-dependent on the uptake of the UC@Si@TA-Cu.In addition,with the extension of time,the pH-sensitive shell was degraded,doxorubicin release was increased,and both the fluorescence of doxorubicin and up-conversion fluorescence were enhanced. |
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