Design And Fabrication Of Stimuli-Responsive Nanoprobes For Cancer Theranostics

As an integration of therapy and diagnosis,the theranostics platform has potential application in personalized medicine,which has attracted more and more attention in recent years.Stimuli-responsive nanoprobes with high efficiency and specificity have broad clinical application in cancer theranostics by taking advantage of the characteristics of tumor microenvironment(TME)and the input of external field sources(light,ultrasound,magnetic,etc.).In this dissertation,we demonstrated the TME-or external stimuli-responsive nanoprobes,including the target miRNA-induced self-assembly of nanoprobes for intracellular amplified Raman imaging of miRNA,the external light-excited nanoprobes for enhanced photodynamic therapy(PDT)with tumor hypoxia relief,and the overexpressed glutathione(GSH)-reponsive nanoprobes for targeted chemodynamic therapy(CDT)with magnetic resonance imaging(MRI)real-time monitoring.The main contents of the dissertation are as follows:(1)Target-induced self-assembly of Au nanoprobes for high-sensitive surface enhanced raman scattering(SERS)detection and imaging of intracellular miRNA.A miRNA-triggered catalytic hairpin assembly(CHA)-induced core-satellite(CS)nanostructure with multiple hot spots and strong electromagnetic field in nanogaps is designed.Intracellular accurate and sensitive miRNA SERS imaging detection in different cell lines with distinct different miRNA expression levels are achieved.The proposed SERS platform contributes to engineering metallic nanoparticle aggregates with strong electromagnetic intensity and has potential application in quantitative and precise detection significant intracellular molecules.(2)Plasmon-induced resonance energy transfer(PIRET)enhanced PDT with Au@SiO2@Cu2O/perfluorohexane nanoprobes.We introduce an efficient inorganic photosensitizer for PDT.By utilizing the PIRET process from Au to Cu2O,the Au@SiO2@Cu2O(ASC)demonstrates a high singlet oxygen(1O2)quantum yield under irradiation.The ASC is loaded into oxygen self-enriched perfluorohexane droplets and coated with liposome to form Lip(ASC/PFH)nanocomposites.The achieved Lip(ASC/PFH)shows considerable anti-cancer efficacy for in vitro cancer cells and in vivo tumor growth.The proposed oxygen self-enriched PIRET-PDT concept has significant implication in PDT design.(3)GSH-responsive biomimic copper/manganese silicate nanospheres(mCMSNs)for synergistic CDT and PDT.Together with photosensitizers,Fenton agent provider and MRI contrast effect along with the response to GSH and tumor targeting ability,allow mCMSNs to realize MRI-monitored enhanced CDT/PDT synergistic therapy.It provides a paradigm to rationally design TME-responsive and reactive oxygen species-involved therapeutic strategies based on a single polymetallic silicate nanomaterial with enhanced anticancer effect.