| Nanoparticle-based drug delivery systems(DDS)have been used for clinical applications ranging from oncology to cardiovascular diseases.These nanomedicines have improved treatment abilities because of their altered pharmacokinetics and biodistribution profiles.The environmental responsiveness of nanoparticles(NPs)has been particularly explored to obtain the desired and high therapeutic efficacy.When exposed to external stimuli,the property changes of NPs favor the release of a drug at the target site.These external stimuli may be a physical signal such as light,temperature,magnetic field and ultrasound,or a chemical signal such as p H,ionic strength,redox potential and enzymatic activity.Considerable efforts are currently being exerted to develop more efficient and safe DDS that provide therapeutic levels of drugs in specific organs,tissues,even cellular structures,where and when required.Although the development and application of them involves some inevitable barriers(such as chronic toxicities,long-term stability,understanding of the biological fate or physiochemical properties,biodistribution,effect in the biological environment,circulation properties and targeting efficacy in vivo),the construction of stimuli responsive drug carriers using biologically safe materials,followed by hydrophilic modification,bioconjugation,targeting functionalization,and detailed safety analysis in small/large animal models may be the best way to overcome these barriers.Mesoporous silica nanoparticles(MSNPs)have been extensively studied as therapeutic drug nanocarriers because of their unique features such as tunable pore size,relative high surface area,excellent stability,favorable biocompatibility,and easy surface functionalization.Because of their nanoscale size,the blood circulation time of MSNPs could be significantly prolonged,and at the same time,they could be selectively accumulated at the tumor sites via the enhanced permeability and retention(EPR)effect.In regard to the biosafety issues in clinic,it is desirable to use lower amount of drug nanocarriers with higher drug loading capability for the drug delivery application.In the last decade,various stimuli-responsive polymers have been utilized to functionalize MSNPs so as to control the release of loaded drugs.Compared with widely reported MSNPs functionalized with inorganic nanoparticles,organic compounds,or biological species,MSNPs coated with responsive polymers are of special interests due to the diversity,multifunctional capability,and excellent drug-controlling capacity of the polymer structures.An approach consisting of core-shell MMSNPs was designed to release loaded substances in response to dual external signals via exploi ting beta-cyclodextrin(?-CD)as an excellent gatekeeper for the silica pores.Ibuprofen(IBU)as an anti-inflammatory drug was easily encapsulated into the nanocarrier with a high loading capacity,and quickly released in response to the stimuli of reduci ng agent or UV light.Interestingly,the magnetic core can enhance the release process through magnetic guiding and pushing the nanocarriers to the targeted sites by using an external magnet or a directed magnetic field.The importance of this study lies i n the possibility that the as-prepared nanocarriers could be more efficacious DDS against some diseases such as pain,fever,and inflammation through dual responsive effects compared with single ones.Also,to provide a wider range of possibilities for the magnetic resonance imaging(MRI)due to the presence of magnetic core(iron oxide nanoparticles).In an effort to further improve chemotherapeutic performance,two or more stimuli-responsive mechanisms could be practically combined into one drug delivery system to meet various requirements under complicated physiological environment.Notably,these multistimuli-responsive drug delivery systems possess all the advantages of individual stimulus approaches at the same time,showing unprecedented control over drug delivery to pathological sites for subsequent drug release.The multi-response design is not only capable of responding to individual stimulus for controlled drug release,but also exhibits enhanced release when triggered with multiple stimuli simultaneously.Nevertheless,only very few studies reported MSNPs-based nanocarriers with more than two stimuli-responsive pathways.Therefore,this work aims to synthesize and investigate a nanocarrier consisted of core-shell magnetic mesoporous silica nanoparticles(MMSNPs),based on triple stimuli-responsive materials designed to release loaded substances in response to external signals.Doxorubicin(DOX)as an anticancer drug was easily encapsulated into the nanocarrier with a high loading capacity,and quick ly released in response to the stimuli of reducing agent,magnetic or hyperthermia.The advantage of such work lies in the possibility that the new nanocarrier could be more efficacious drugs against some tumor cells by triple responsive effect compared with single or dual stimuli responsive ones.Moreover,p H-responsive nanocarriers based on MSNPs modified with poly(3-methacryloxypropyltrimethoxysilane)“PMPS” and the p H-sensitive polymer: poly(N,N-dimethylaminoethyl methacrylate)“PDMAEMA” were constructed,characterized and tested to evaluate their efficacy as DDS.The grafted PDMAEMA served as efficient gatekeeper to adjust the encapsulation and in vitro release of an anticancer drug loaded inside the pores by altering p H values of the medium.These hybrid nanoparticles showed a high loading capacity with quick release in acidic p H,which exists mainly in the diseases environments e.g.inflammatory and cancerous sites.In addition,thermal and CO2 dual-stimuli were applied in this system,too.The smart PDMAEMA acted as active cap to adjust the loading or in vitro release processes of a fungicidal drug loaded inside the mesopores by altering temperature or CO2 of the tested environment.More interestingly,treating the nanomaterials by CO2 for few minutes was found to have a bactericidal effect with promising results as indicated by the disk diffusion technique.In general,the positive biological activity against selected strains of bacteria and fungi indicates that,these particles may be helpful for engineering more efficient antifungal or antibacterial agents for pharmaceutical applications. |
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