Hypoxia Response Nanoprobe Used For Tumor Imaging And High Performance Therapy

Cancer,as one of the major threats to human health in the world,originates from normal tissues.The similarity between normal tissues and cancerous tissues complicates the diagnosis and treatment of cancer.Nevertheless,early detection of disease can significantly reduce cancer mortality.Therefore,early diagnosis is very important to improve the prognosis of cancer patients.Currently,clinical detection of cancer mainly relies on imaging technology or morphological analysis of suspected diseased cells(cytology)or tissues(histopathology).Fluorescent probes are attractive universal tools for both analytical sensing and optical imaging because of their high sensitivity,fast response time,and technical simplicity.Fluorescence imaging technology is therefore important to the early diagnosis of tumors.With the development of oncology in biology and biomedicine,it has been proved that abnormal physiological and chemical conditions and imbalanced biosynthetic intermediates in tumor microenvironment(TME)play a key role in making tumor cells resist or evade the damage caused by traditional clinical cancer therapy(including surgery,chemotherapy,radiotherapy,etc.).Hypoxia,as one of TME,can promote the growth,invasion,metastasis and apoptosis of cancer cells.Studies have shown that hypoxia in various types of cancer is actually associated with high proliferation and invasive phenotypes mediated by hypoxia inducible factor-1?(HIF-1?).Upregulation of HIF-1? expression induces the transcription of various downstream genes,which play an important role in tumor progression.Downstream genes guide the adaptation and survival of tumors under hypoxic conditions.The application of nanotechnology in cancer diagnosis has great prospects in improving the sensitivity and versatility of fluorescence detection methods.In summary,the specific work of this paper is as follows:1.Hypoxia-Responsive Nanoprobe for Tumor Genetic and Photodynamic Synergistic TherapyIn this chapter,we construct a novel nano-inhibitor that controls the release of anti-HIF-1? in response to azo reductase to overcome the limitations of PDT-induced hypoxic-enhanced anti-cancer therapy.AuNPs@?CD was obtained by modifying SH-?CD on the surface of AuNPs,then designed a double-stranded DNA/RNA hybridization complex(DRHC)consisting of the HIF-1?-against RX-0047,in whichAS1411 was linked to DRHC via azobenzene.AuNPs@?CD@DRHC was obtained by the interaction between AuNPs@?CD and DRHC.Aptamer AS1411 forms G-quad chains combined with cationic porphyrins 5,10,15,20-quad(1-methyl-4-pyridinyl)-21 h,and 23h-porphyrins(TMPyP4)by ?-? interaction to undergo photodynamic therapy(PDT)under light.After entering the tumor cells,under the light,the tumor cells further release DRHC under hypoxia for gene therapy.Combination therapy can effectively inhibit and kill cancer cells.2.Hypoxia-responsive Metal-organic Frameworks-based Nanoprobe for Tumor Chemo-and Genetic Synergistic TherapyIn this chapter,we constructs a nanoprobe that responds to azoreductase-controlled release of anti-HIF-1? and the chemotherapy model drug doxorubicin(DOX),thereby inhibiting DOX efflux enhancement of chemotherapy.Firstly,the DOX-loaded nanoprobe DOX@AMOFs was synthesized by one-pot method,and the double-stranded DNA/RNA hybrid complex(DRHC)labeled with fluorophore was adsorbed on the nano drug by electrostatic interaction to form nanosensor DOX@AMOFs@DRHC,DRHC consists of RX-0047 against HIF-1?.In response to the hypoxic microenvironment of tumor cells,the nanosensor dissociates and releases the drug DOX and anti-HIF-1? siRNA for chemical and gene combination therapy,while siRNA can inhibit the expression of P-gp and MRD1 and reduce drug efflux enhancement chemotherapy.