Fabrication Of Multifunctional Carbon Nanoparticles For Diagnosis And Phototherapy Of Tumors

Cancer has become one of the biggest challenges in the present-day world,during the last two decades,various types of nanomaterials have been developed and investigated for cancer theranostic applications.Among the various types of nanomaterials,carbon-based nanomaterials,because of their unique physicochemical properties,have been extensively explored as efficient multifunctional theranostics agents.Mesoporous carbon nanospheres(MCNs)can carry a large amount of drugs due to their remarkable pore volume and specific surface area,and have strong absorption in the near-infrared region(NIR),showing great potential in nanomedical applications.However,high-temperature calcination during their preparation makes this material very easy to aggregate,and the synthesis process is complicated,which hinder their further application.In addition,carbon dots(CDs)have shown tremendous potential for a wide range of applications,especially their amazing luminescence,small sizes,low toxicity,high hydrophilicity and excellent biocompatibility.Recently,more and more researchers are devoting themselves to the development of metal-encapsulated CDs to give them more excellent properties and widen their application.However,doped CDs always undergo some drawbacks in the field of biomedicine,their single properties can not meet the needs of theranostics.In Chapter 2,we synthesized hollow and mesoporous carbon nanospheres(HMCNs)with uniform size on a large scale through a template-free strategy,and improved the dispersibility of HMCNs by wet oxidation.The properties of hollow cavity and mesoporous structures make the HMCNs achieve high drug loading(48.0 wt%).The near infrared(NIR)absorbance achieve excellent photoacoustic imaging ability and photothermal conversion efficacy(32.0%).The investigations in vitro and in vivo demonstrated that HMCNs can perform strong PA imaging,and induced great tumor inhibition by the combination of chemotherapy and PTT.However,the MCNs which have a relatively large size are difficult to be cleared out of the body post-treatment.In order to solve this problem,in Chapter 3 and 4,we successfully synthesized Gd-encapsulated and Mn-encapsulated CDs which are sub-10 nm nanoparticles,they can be efficiently excreted through renal clearance,causing little to no long-term toxicity to the host.In addition to the fluorescence properties and magnetic resonance imaging(MRI)properties,Gd-encapsulated CDs with wide absorption in the NIR can effectively produce singlet oxygen under light irradiation,which can be used for photodynamic therapy(PDT).Both in vitro and in vivo experiments indicated that Gd-encapsulated CDs were unique nanotheranostic agents intrinsically integrated with fluorescence,MRI and PDT properties.In Chapter 4,a novel fluorescent Mn-encapsulated CDs(Mn-CDs)with high stability,excellent solubility and superhigh T1 relaxivity compared with similar Mn-based contrast agents.Moreover,the Mn-CDs not only exhibited tunable full-color emission but also passed through blood-brain barrier(BBB),showing high selectivity and enrichment in glioma cells without the aid of any extra targeting molecules.Studies in vivo with rodent tumor models demonstrate the promise of Mn-CDs as dual fluorescence imaging and MRI for precise brain cancer diagnostics.The research in this paper provides new insights and great application prospects for the design of carbon nanomaterials as new novel multifunctional probes for cancer diagnosis and therapy.