Exploration Of Photothermal Agents With High Efficiency For Therapy Of Cancers

Photothermal therapy is a new technology for cancer treatments emergently developed in recent years. Its working principle is using the near infrared laser light which has good permeability for biological tissue to irradiate the photothermal agents, to generate high fever in partial position to induce cancer cell death and tumor degradation. This oncology technology is very popular because of its simple and controllable features with low side-effects. Photothermal agents play pivotal roles in the oncology technology for its innovation. With the continuous development of nanotechnology, nanomaterials have made more and more utilization in cancer treatments. Majorable NIR-response nanomaterials and nanocomposites are explored for photothermal therapy and combined therapies of cancers.In this dissertation, firstly, the author introduced briefly about the technology of photothermal therapy, discussed their possible mechanisms of light absorption by the photothermal agents, and review the recieved progress of photothermal agents in recent years, to guide directions to explore new photothermal agents with low toxicity, high photothermal efficiency and versatile functions. After that, the author provided specific researches as practical strategies for overcoming some obstacles of photothermal agents, such as low photothermal conversion efficiency, complexly synthetic protocol, high toxicity and singleness of function. The specific works are as follows:?1? Tunable synthesis of hydrophilic Bi₂S₃ nanoflowers with high photothermal conversion efficiency for photothermal ablation of cancer cellsBismuch-based nanomaterials have been explored as photothermal agents but with low photothermal conversion efficiency. Herein, hydrophilic Bi₂S₃ nanoflowers and Bi₂S₃ nanobelts were prepared by a one-pot solvothermal method. We found that the PVP not only changed morphologies of the product from nanobelts to nanoflowers, but also influenced their colloidal dispersion, crystallinity as well as NIR-absorption. Moreover, photothermal conversion efficiency of the Bi₂S₃ nanoflowers is doubly?64.3%? higher than the Bi₂S₃ nanobelts?36.5%? and the gold nanorods?54.3%? upon irradiation of an 808-nm laser. Therefore, the Bi₂S₃ nanoflowers could trigger rapidly cellular deaths upon irradiation of a NIR laser in vitro and in vivo. High photothermal performances of the Bi₂S₃ nanoflowers should be mainly attributed to the three aspects. Firstly, the Bi₂S₃ nanoflowers exhibited intense NIR-response with a high mass extinction coefficiency(20.5 L?g^-1?cm^-1) at the excitation wavelength?808 nm?. Subsquently, three-dimensional superstructure of the Bi₂S₃ nanoflowers with a large surface could serve as laser-cavity mirrors with improved reflection, refraction, and absorption of photoelectrons, leading to extend the interaction time between the photoelectrons and the material thus to enhance their utilization for photoelectrons. Finally, the Bi₂S₃ nanoflowers had a narrower bandgap?Eg = 0.79 eV? to further improve their absorption of low-energy light. The above results should pave approaches to explore new photothermal agents with high photothermal efficiency.?2? Hydrous RuO₂ nanoparticles as a new type of photothermal agent for cancer therapyGreen synthesis of nanoparticles with low toxicity is an important issue for their bioapplications. Herein, hydrous ruthenium dioxide?RuO₂?xH₂O? nanoparticles with good NIR-absorption were prepared by one-pot hydrothermal method from hydrolysis of the RuCl₃?xH₂O precursor. NIR-response of the prepared RuO₂?x H₂ O nanoparticles could be attributed to their absorption/desorption of water and protons along with charge transitiones between various ruthenium redox pairs, resulting in them with a unique extinction in aqueous solution. After surface-modification of PVP, the product?PVP-RuO₂? exhibited low cytotoxicity, excellent dispersion in physiological medium and high photothermal conversion efficiency 54.8% by an 808-nm laser induced. In particular, the PVP-RuO₂ nanomaterials could reach a rapid increasing of temperature to efficiently kill of cancer cells in vitro and in vivo, and to seriously inhibit tumor growths. Therefore, the RuO₂?x H₂ O nanoparticles can be utilized as a potential new type of photothermal agent for hyperthermia therapy of cancers.?3? Preparetion of the FeWO₄@PPy nanocomposites with core/shell structure for cancer theranosticsDiagnostic results can guide the therapeutics of cancers. According to previous reports, polypyrrole?PPy? is a well biocompatible and biodegradable photothermal agent with high photothermal performance but simple function, and FeWO₄ is a predicted MRI/CT dual-modal contrast agent but with low photothermal performance. While combining the two cheap and facilely synthetic materials into an individual construction, it would be a possible versatile nanoplatform for cancer diagnostics and therapeutics.Herein, FeWO₄ nanoparticles were firstly prepared by hydrothermal method and then in-situ surface-polymerization of PPy shells to fabricate inorganic/organic hybrid FeWO₄@PPy nanocomposites with core/shell nanostructures. The FeWO₄@PPy nanocomposites performed effect MRI/CT contrast ability in solution, with a transverse relativity?r2? of 1.46 mM^-1?s^-1, and an X-ray attenuation coefficient of 12.99 HU?mM^-1. The later is even higher than the coefficient of iohexol(5.74 HU?mM^-1). Thus, HeLa tumors in mice injected with the nanocomposites could be distinguished with significant enhancement of MRI/CT signals. Blood circulation and tissue distribution studies indicated that the intravenously injected FeWO₄@PPy nanocomposites could be completely cleared out from the blood within 4 hours by the reticuloendothelial system, with high accumulation in liver?67.2 ± 1.8% ID/g? and spleen?33.1 ± 5.0% ID/g?. The nanocomposites could be also enriched in tumor sites?1.2 ± 0.4% ID/g? arising from the specific EPR effect of tumors. Additionally, upon irradiation of an 808-nm laser, the nanocomposites can generate enough thermal energy?photothermal conversion efficiency 56.1%? to kill of cancer cells hence to seriously inhibit the tumor growths. All in a word, the FeWO₄@PPy nanocomposites exhibited great potential applications in multimodal imaging diagnosis and photothermal therapy of tumors.