Study On The Applications Of Albumin Composite Nanoparticles In Multimodal Imaging Guided Tumor Photothermal Therapy

In recent years,nanomaterials have been attracting much more attention as a new theranostic platform for cancer diagnosis and therapy.Researchers have designed a variety of nanostructures to achieve multimodal imaging combined with multiple therapy for enhancing diagnostic accuracy and therapeutic efficiency.Such multifunctional materials were usually prepared by chemical coupling,co-packaging and other methods,due to the prevalence of complex,difficult preparation,limited load capacity,lack of targeting and poor imaging or treatment and other issues,consequently exploring and developing efficient,simple,green multifunctional nanoparticle synthesis is still a major challenge.Albumin template-mediated bio-mineralization has the advantages of simple,reproducible,good biocompatibility and stability,and has good application prospect in clinical diagnosis and therapy.Studies have shown that Gd₂O₃ albumin nanoparticles exhibit excellent MRI angiography,and Bi₂S₃ albumin nanoparticles can be used to guide the photothermal therapy with CT/PA imaging due to strong X-ray attenuation and near-infrared absorption.Photothermal therapy（PTT）has been considered to be a great potential for cancer treatment because of its noninvasive,targeting and high efficiency.The principle of PTT is to convert the near-infrared（NIR,700-1100 nm）light absorbed by the photothermal-converted nanomaterials in tumor cells to heat,leading to thermal ablation of tumors.However,most of the reported protein nanoreactors contain only a single reaction to obtain a single component product,resulting in a lack of treatment or diagnostic performance that requires further modification in order to obtain more imaging and therapeutic functions.On the basis of this,we developed a method of synthesizing two kinds of functional nanoparticles in the same protein template,and prepared with magnetic resonance,photoacoustic,CT trimodal imaging and photothermal therapy functional protein nanoparticles.The nanoparticles showed good tumor targeting in tumor-bearing animal models,and could be used for magnetic resonance,photoacoustic and CT imaging to achieve all-round,high-precision imaging precisely guided treatment efficiently.The details of the study are as follows:Firstly,recent research progresses of multifunctional nanomaterials in tumor diagnosis and therapy were briefly introduced.The basis and mian contents of this thesis were expounded.Then,bovine serum albumin was used as nanoreactors to induce bismuth and gadolinium ions in the cavity of protein.The albumin complexes of bismuth sulfide/gadolinium sulfide were prepared by adjusting the reaction conditions to optimize the preparation process.The results showed that DCNPs were homogeneous spherical structures with an average size of 4.54±0.82 nm.The DCNPs possessed superior near infrared absorption,significant photothermal conversion,potent photothermal capability,ideal physical and chemical stability and photostability,as well as enhanced PA/MR/CT signals.In vitro cytology evaluation results showed that DCNPs could be effectively ingested by tumor cells and were mainly located in lysosomes.DCNPs with inherent biocompatibility could specifically kill tumor cells(IC₅₀ 0.71 mM)under irradiation.Finally,the tumor model was established by 4T1 cells.In vivo evaluation displayed that DCNPs exihibt desirable tumor accumulation at 12 h post-injection.The results of in vivo imaging showed that DCNPs possess higher sensitivity and higher contrast near-infrared fluorescence imaging and photoacoustic imaging.DCNPs also presented enhanced CT/MR imaging contrast compared with Iopromide and Gd-DTPA,further resulting in complementary MR imaging with high spatial resolution and CT imaging with macroscopical anatomic information.With a single dose of DCNPs(10μmol kg^-1 Bi),the temperature of tumor site increased by 18.7℃after laser irradiation during 12 h post-injection,which could effectively ablate the tumor without recurrence.Long-term toxicity studies had shown that DCNPs were highly biocompatible and safe,and could be cleared by the metabolism of the body without damage to normal tissues.In summary,we presented dual-component nanoparticles synthesized by controlling two simultaneous reactions in the same protein nanoreactor for complementary multimodal imaging and efficient tumor ablation,and we further explored the applications in the field of cancer theranostics,which would have promising potentials in clinical cancer therapy.