Dendrimer-entrapped Gold Nanoparticles Loaded With ⁶⁸Ga And CpG For PET/CT Dual-modality Imaging And Immunotherapy

In recent years,due to the increasing morbidity and mortality,cancer has become threaten to human’s health.Therefore,the early diagnosis and efficient treatment is an effective way to improve the survival rate of cancer patients.In clinical,X-ray computed tomography（CT）,magnetic resonance imaging（MR）and ultrasonography（US）play a pivotal role.With the development of nuclear medicine imaging,positron emission tomography（PET）imaging has received widespread attention because of its advantages in early diagnosis.PET shows significant advantages in biometabolic detection,but it lacks structure imaging effect,which limits location of the lesion.By combining PET and CT imaging,it can clearly observe the structural and molecular level changes of lesions,which has attracted great interest from researchers.On the other hand,traditional tumor treatments such as chemotherapy,surgical treatment and radiotherapy cannot completely cure tumors and have certain side effects on patients.With the development of immunology and molecular biology,immunotherapy has rapidly emerged and is considered as one of the most effective treatments for tumors.It can inhibit the growth of tumors by activating the patient’s own immune system.The development of nanotechnology has promoted the application of nanomaterials in cancer diagnosis and treatment.Among many nano materials,dendrimers（PAMAM）are widely used as carriers to load contrast agents or therapeutic agents for tumor diagnosis and treatment because of their modifiable functional groups and large hydrophobic cavities.In this paper,we report the design of a novel nanoplatform based on glucose-modified dendrimer-entrapped gold nanoparticles（Au DENP）incorporated with radionuclide ⁶⁸Ga and cytosine-guanine（CpG）oligonucleotide for positron emission tomography（PET）/computed tomography（CT）dual-modality imaging and immunotherapy.In Chapter 2,we first modified the chelator DOTA and the targeting molecule DG-PEG on the surface of G5 PAMAM,and then entrapped gold nanoparticles in its internal cavity to form DG-Au DENPs.The characterization results proved that the nanomaterial DG-Au DENPs had uniform size distribution,good colloidal stability,efficient radioactive element labeling efficiency,good radioactivity stability,and good gene compression ability.In Chapter 3,through in vitro experiments,we demonstrated that the nanomaterial has good biocompatibility and excellent cancer cell targeting ability,which can efficiently mature dendritic cells and further activate T cells for tumor cell killing.In Chapter 4,the material can be successfully used for targeted PET/CT dual-modality imaging and immunotherapy in the mice melanoma models.These findings suggested that the designed ⁶⁸Ga-labeled DG-Au DENPs may hold a great promise as a novel theranostic nanoplatform for targeted cancer imaging and therapy.