Stimulation-responsive Gold Nanoparticle Self-assembly Technology For Photothermal Therapy Of Tumor

In recent years,the development of nanomaterials in the field of cancer treatment has been very rapid,providing many new perspectives for cancer treatment.Among many nanomaterials,gold nanoparticles(AuNPs)are widely used as tumor diagnosis and treatment(diagnosis and treatment)materials,and are widely used in the research of tumor photothermal therapy(PTT),radiotherapy and photoacoustic imaging(PAI).The researchers found that small-sized AuNPs tend to have longer blood circulation and stronger tissue penetration,and are more suitable for the diagnosis and treatment of tumors.However,due to the small size,AuNPs can easily return to the blood or transfer to the surrounding tissue after entering the solid tumor,which greatly reduces the concentration of particles in the tumor site.The large-sized AuNPs are not easy to penetrate blood vessels and are trapped in the cytoplasm,which is more conducive to their enrichment at the tumor site.However,for spherical AuNPs,only particles with a diameter greater than 50 nm can strongly absorb near-infrared light(NIR)for photothermal therapy.Therefore,in order to solve the above difficulties,small-sized particles can be self-assembled to form large-sized nanoparticle aggregates in the body.So far,AuNPs can self-assemble or aggregate through electrostatic interactions,DNA-mediated and chemical reactions,but there are still deficiencies in the targeted treatment of tumors.Therefore,this paper aims to use stimulus response sources to induce AuNPs to undergo controlled aggregation to achieve the purpose of photothermotherapeutic treatment of tumors,and carries out the following two tasks:1.A metal-organic framework based nanocomposite with co-encapsulation of DNA-gold nanoparticles and doxorubicin for pH-triggered synergistic chemo-photothermal treatment of cancer cellsSynergistic heat therapy is one of the most effective cancer treatment strategies.Zeolite-like imidazolate(ZIF-8),as one of the metal organic framework(MOFs)materials,is composed of Zn²⁺and 2-methylimidazolium salt,which has the characteristics of flexibility and large loading capacity,and has become an anticancer drug Potential carrier.Taking advantage of the ability of ZIF-8 to degrade under acidic conditions,it is proposed to construct a pH-responsive composite nano-system of ZIF-8-encapsulated DNA-functionalized AuNPs and anti-tumor drugs,which can be used for the response of solid tumor tissues to a slight acid environment.Controlled drug release and photothermal therapy.In this system,two complementary DNA single strands were modified on the surface of AuNPs,combined with anti-tumor drugs,and wrapped in ZIF-8.ZIF-8 is stable under physiological conditions,while under acidic conditions,the structure of ZIF-8 is destroyed and decomposed,thereby releasing antitumor drugs and two functionalized AuNPs.Functionalized AuNPs become large aggregates due to the complementary effect of DNA.It is expected to enhance the photothermal conversion efficiency under laser irradiation,combined with the role of chemotherapy to achieve better tumor killing effect and provide new ideas for tumor treatment.2.Aggregation of gold nanoparticles based on catalytic hairpin self-assembly technology for photothermal therapy of tumorsStudies have shown that MicroRNA(miRNA)is one of the emerging biomarkers for early diagnosis and prognosis of human cancer,and has high expression levels in most tumors.Here we continue to take the stimulus response source as the starting point,focus on the highly expressed miRNA in the tumor,and plan to construct a miRNA-induced gold nanoparticle aggregation system for photothermal therapy of tumor.In view of the low abundance of miRNA,we designed the introduction of catalytic hairpin self-assembly technology(CHA),modified the hairpin DNA H1 and H2 on the surface of AuNPs,and planned to build a binary system that can be used in the CHA cycle.In the presence of miRNA,the CHA reaction can generate a large number of DNA double-stranded hybrids.The distance between the AuNPs connected to the DNA is shortened to form large aggregates.It is expected that more heat energy will be generated under NIR irradiation to achieve tumors.Photothermal therapy.In order to improve the aggregation of gold nanoparticles,miRNA-21 was proposed as the target,and the CHA system was first optimized.This method is expected to provide new ideas for the aggregation of gold nanoparticles and the quantification of miRNA,and further promote the application of AuNPs in the integration of tumor diagnosis and treatment.