Multifunctional Nanotheranostics For Magnetic Resonance/Fluorescence Bimodal Imaging-Guided Cancer Combined Photo/Immuno-therapy

Currently,it is very promising to develop the nanotheranostics that integrate the diagnostic and therapeutic functions into a single nanocarrier for more accurate and effective cancer treatment.As a new technique,phototherapy has rapidly become a research hotspot due to its high selectivity,non-invasiveness,controllability and potential stimulation on immune systems.So it is very fascinating to combine the phototherapy with immunotherapy to maximum the therapeutic efficiency.On the other hand,the single diagnostic method?such as magnetic resonance imaging?MRI?,fluorescence imaging?FI??often has limitations in the clinical applications because of the detection depth,sensitivity and resolution.Based on these,it is highly required to design new multifunctional photo-immuno nanomedicines guided by multimodal imaging for precise,complete and safe elimination of cancer.In this thesis,a new type of nanotheranostics with both MRI/FI and photo/immunotherapy functions was fabricated by self-assembling the photoactive graphene quantum dots?GQD?,immune adjuvant CpG nanoparticles and MRI/FI imaging probe.Firstly,GQD were modified with photosensitizer Chlorine6?Ce6?and polydopamine to form the negatively charged GQD-Ce6-pDA?termed as GCpD?.Meanwhile,polylysine?PLL?and CpG formed the positively charged nanoparticle PLL/CpG?termed as P/C?through electrostatic interaction.After forming the P/C@GCpD,Gd³⁺was further chelated to obtain P/C@GCpD?Gd?theranostics.It owned a regular spherical shape with the hydrodynamic diameter of about 190 nm,strong fluorescence signal,and a relaxation rate up to 42.6 mM-1s-1.The biological assays demonstrated that P/C@GCpD?Gd?could not only effectively kill tumor cells through phototherapy,but also stimulate the immune cells to release the pro-inflammatory cytokines such as TNF-?and IL-6.Moreover,P/C@GCpD?Gd?effectively accumulated at the tumor site,allowing high-quality MRI/FI bimodal imaging in-vivo.Upon activation by 660nm laser,P/C@GCpD?Gd?achieved the synergistic inhibition efficiency on EMT6 breast tumor compared with the single phototherapy or immunotherapy.This study demonstrated the potent prospect of the hybridnanomedicineP/C@GCpD?Gd?withMRI/FIdualimagingand photo-immunotherapy capabilities in the precise treatment of tumor.