Biomedical Application Of Theranostic Metal And Metal Oxide Nanoparticles

Nowadays, several problems have been observed in clinical trials. One of these is the global prevalence of antibiotics resistance pathogens, which possess great threaten to public health. Lack of reliable characterization assay for accurate detection leads to abuse of antibiotics in clinical trials, which failed to exert therapeutic effect in some cases and contributed primarily to the formation of super-bacterias. Another obstacle is the war against cancer. Traditional ways to tackle tumor burden mainly rely on three methods:radiotherapy, chemotherapy and surgery, side effects plus low cost effectiveness always lead to sub-optimal therapeutic outcomes. Finding potential personalized treatment integrating lesion specificity and negligible invasiveness is of great research and clinical practice significance.With the rocket up of nanoscience, combination of nanotechnology with traditional medicine has created a new discipline named nano-medicine. With the emerging methods for surface modification of nanomaterials, targeting delivery capability could be easily achieved via surface conjugation of antibodies. CT contrast agents based on high atomic number metal elements greatly enhanced the X-ray attenuation efficacy and contributely primarily to the field of non-ianvasive imaging. By taking advantage of specific nanomaterials. photons could be absorbed and converted into phonons, which lead to obvious heat generation. Thanks to the deep tissue penetration of NIR light, tumor or other lesions in organs could be treated with photothermotherapy （PTT） in a light controllable manner. Besides, PTT armed with probes or contrast agents to construct theranostic platforms, which integrating both contrast imaging and therapeutic potency, have attracted great research interests in oncological trials.In this thesis, we firstly investigated Au@Ag core-shell structure nanoparticles as targeting platform against methicillin resistant Staphylococcus aureus （MRSA） pathogen induced pneumonia and in vivo anti-inflammatory performance. After that, we have developed two kinds of non-stoichiometric tungsten oxide nanoparticles with different kinds of surface modifications. Capability to specifically eliminate HER-2 positive metastatic lymph nodes under CT guidance or integrating immunotherapy with PTT to conquer tumor were validated separately. Details were provided as following:（1） Au@Ag nanoparticles were synthesized via one-pot method. Inner Au core contributed mainly to X-ray attenuation and act as contrast agent for CT imaging. Outer silver nanoshell inhibited the proliferation of MRSA via direct contact with bacterial membrane. In this study, we are interested in the potential of targeting Au@Ag nanoparticles to detect MRSA induced pneumonia and in vivo anti-inflammatory performance. This novel targeting platform integrating both diagnostic and therapeutic potency would shed light on the development of novel non-invasive assay for clinical practices.（2） Non-stoichiometric tungsten oxide nanoparticles (W₁₈O₄₉NPs) were fabricated via polyol method. Surface conjugation between antibodies and carboxyl groups of W₁₈O₄₉ NPs further rendered the platform with HER-2 antigen specificity. Owing to superior X-ray attenuation and characteristic NIR light absorption property, W₁₈O₄₉NPs could be taken as a novel theranostic platform. On this basis, therapeutic outcome was analyzed in HER-2 positive metastatic lymph nodes post targeting PTT under CT guidance. We hope this robust theranostic platform could play an active role in non-invasive diagnosis and treatment in clinical trials.（3） By taking advantage of the same nanoparticles (W₁₈O₄₉ NPs). we used anti-CD39 antibodies instead of anti-HER-2 antibodies and created a regulatory T cells （Tregs） targeting platform. Different from we mentioned above, we changed the target of our treatment from tremendous cancer cells to tumor infiltrated Tregs and designed a new method named Treg targeting immuno-PTT. Treg specific immune-PTT significantly reduced the dosage of W₁₈O₄₉NPs with respect to traditional PTT. In addition, Treg immune-PTT merits from both immunotherapy and PTT, could stimulate anti-tumour immunity and destroy tumor immune-suppresive network simultaneously. Such kind of multi-functional platform for immune-PTT was expected to play a pivotal role in clinical translation of immunotherapy.