DNA Functionalized Hollow Mesoporous Silica Nanoparticles For Near-Infrared Responsive Synergistic Tumor Therapy

The rapid development of nanomaterials provides promising approach for tumor therapy.Compared with traditional chemotherapeutic drugs,the functionalized nanomaterials as drug delivery system can greatly increase the local effective therapeutic concentration in tumor but not in normal tissue.Moreover,the functionalized nanomaterials can realize a "zero premature release" and release the encapsulated drugs into designed locations.In addition,effective synergistic treatment can be designed,and this synergistic treatment could offer obviously a better therapeutic effect compared to monotherapies.As one of the promising nanosized drug delivery system,mesoporous silica nanoparticles(MSNs)have unique features such as tailorable mesoporous size,good diversity in surface functionalization,fantastic biocompatibility,high specific surface area and low toxicity.All of these merits contribute to the widespread studies and applications of MSNs in tumor therapy.Nonetheless,despite remarkable progress in the past years,MSNs cannot satisfy the extension of applications in biomedical research due to their limited loading capacity.Compared with conventional MSNs,HMSNs has vast empty interior cavities to accommodate large quantities of therapeutic agents,which provides opportunities for an ultrahigh drug loading capacity.In this paper,the functionalized hollow mesoporous silica nanomaterials were combined with phototherapy,chemotherapy and gene therapy to develop a DNA functionalized hollow mesoporous silica nanoscale system for near infrared(NIR)light responsive synergistic tumor therapy.The main research aspects are as below:1.Co-delivery of doxorubicin and indocyanine green into DNA-modified hollow mesoporous silica nanoparticles responsive to near-infrared light for chemo-phototherapyStarting from the zeolitic imidazolate framework-8(ZIF-8)template,a layer of mesoporous silica was coated on ZIF-8(ZIF-8@MSNs)by sol-gel method and subsequently the template was self-degraded under acidic conditions to obtain HMSNs.Thereupon,ICG loaded into HMSNs core and then skilfully coated double strands DNA onto the HMSNs surface for anti-cancer drug DOX intercalation.The obtained near-infrared(NIR)-responsive DOX@DNA-ICG@HMSNs nanotherapeutic system was used to synergistic chemo-photothermal therapy of tumor cells.Specifically,upon NIR laser irradiation,the photothermal effect of DOX@DNA-ICG@HMSNs not only induced photothermal therapy,but also resulted in DNA denaturation and the rapid release of DOX for chemotherapy.Thus,chemo-photothermal synergistic therapy was realized.Due to the huge inner cavities,the loading amount of ICG was determined to be 930 mg g-1 SiO2,which is more than 30 times compared to that in MCM-41-type MSNs.In vitro studies using human cervical cancer HeLa cells demonstrated that the controlled release behavior of DOX@DNA-ICG@HMSNs was NIR laser-dependent in cells by confocal laser scanning microscopy images analysis.Furthermore,MTT assays indicated that the system of DOX@DNA-ICG@HMSNs had the effective synergistic treatment effect,and this synergistic treatment could offer obviously a better therapeutic effect at the cellular level compared to monotherapies.2.Antisense oligonucleotide POY2T-functionalized hollow mesoporous silica nanoparticles encapsulated indocyanine green for near-infrared light triggered gene-photothermal therapyWith the development of genetic engineering,genetherapy has gradually become a promising high-tech industry.In the search of the treatment efficiency of genetherapy,not only need pay attention to the effective of the target gene into the receptor cells,but also need to integrate other effective treatment methods together.Based on the previous work,antisense oligonucleotide POY2T were modified on the surface of hollow mesoporous silica nanomaterials which containing indocyanine green(ICG)and then developed a NIR-triggered sysnergistic gene-phototherapy system,owning to POY2T could bind to the overexpressed c-myc P2 promoter in human breast cancer cells(MCF-7),thereby inhibited expression of c-myc gene in MCF-7 cells.Upon NIR laser irradiation,the photothermal effect of POY2T-ICG@HMSNs not only induced photothermal therapy,but also resulted in DNA denaturation and the rapid release of POY2T for gene therapy.Furthermore,MTT assays indicated that the system of POY2T-ICG@HMSNs had the effective synergistic therapy effect.