Human HSP70 Promoter-Based Prussian Blue Nano-Systems And Their Applications In Thermo-Controlled Tumor Therapy And Diagnosis

The development of nanotechnology has enabled the development of diverse nanomedicines possessing distinct structural features and paves the path for nanotheranostics in tumor diagnosis and therapy applications.Although gene therapy and photothermal therapy have shown great potential for cancer treatments in recent years,both strategies have faced complex problems,such as low therapeutic efficiency and difficulty in precise control of the therapeutic process.Therefore,a multifunctional prussian blue?PB?nanotheranostic platform has been designed to load the therapeutic plasmid DNA?HSP70-p53-GFP?for near infrared light?NIR?-triggered thermo-controlled synergistic gene therapy?GT?and photothermal therapy?PTT?.The specific contents are as follows:?1?Preparation of PEI-modified prussian blue nanocubes and construction HSP70 promoter-based heat-induced gene expression vector.The results showed that PB@PEI NCs have a uniform particle size,stable structure and good photothermal performance,which can be used as gene vectors,photothermal conversion agent.Moreover,PB@PEI NCs provided excellent stability with good longitudinal and transverse relaxation rates,which can be used as MR imaging contrast agent.The plasmid of HSP70-GFP and HSP70-p53-GFP were correctly constructed by sequence analysis;?2?Biosecurity and pharmacokinetic studies of nano-systems.The results showed that PB@PEI/HSP70-p53-GFP NPs could realize effective location in tumor sites due to the enhanced permeation and retention?EPR?effect with good biosecurity and biocompatibility;?3?In vitro thermo-controlled GT/PTT synergistic therapy.The results showed that mild NIR-laser irradiation?⁴1??activates HSP70 promoter for the tumor suppressor p53-dependent apoptosis,while strong NIR-laser irradiation?⁵0??induces photothermal ablation.The significant synergistic efficacy can be achieved by adjusting NIR-laser irradiation?from⁴1?to⁵0??,compared to GT or PTT alone;?4?In vivo thermo-controlled synergistic GT/PTT therapy under MR imaging.The results showed that this nanoplatform can serve as promising T₁/T₂-weighted MR contrast agents due to EPR effect.The combination of GT and PTT induced by PB@PEI/HSP70-P53-GFP NPs resulted in remarkable synergistic effect to achieve almost complete eradication of tumors without visible recurrence.All of the results suggest the synergistic strategy has great potential in simultaneously achieving the control of gene expression and efficient tumor ablation,which may be promising nanotheranostics for thermo-controlled synergistic GT/PTT under MR imaging guidance.