Synthesis And Anticancer Applications Of Metal-doped Carbon-based Nanoparticles

Photothermal therapy,as a noninvasive or minimally invasive treatment modality with high efficiency and few side effects,has attracted increasing attention for cancer therapy.Nowadays,various nanomaterials have been developed as photothermal agents,including metal nanoparticles,semiconductor nanoparticles,carbon-based materials,and other inorganic/organic nanoparticles.Compared with metal nanoparticles,carbon-based nanomaterials（such as carbon nanotubes,graphene and its derivatives,and carbon quantum dots）show lower toxicity and fabrication cost,and thus can be used as promising photothermal agents.However,there are still challenges for their further applications because of their relatively low near-infrared absorption,low cellular uptake,and/or high liver accumulation.This thesis focuses on the synthesis of metal-doped carbon-based nanoparticles and their photothermal conversion efficiency,cellular uptake and transport,tumor-targeting ability,and anticancer efficacy,which will promote the development of novel photothermal nanoagents and deepen our understanding of photothermal therapy.Specifically,this thesis includes the following three chapters:1.Synthesis of copper/carbon quantum dot-crosslinked nanosheets（CuCD NSs）and their application for multimodal imaging-guided photothermal cancer therapy（Chapter 2）.The sulfur-doped carbon quantum dots（CDs）are synthesized using o-phenylenediamine and _L-cysteine as the carbon sources by a hydrothermal route.Utilizing the CDs as both the reductant and the template,the CuCD NSs are obtained through simply mixing Cu²⁺solution and CD solution.The obtained CuCD NSs show several advantages,including excellent photothermal conversion efficiency,good photothermal stability,proper size（20–30 nm）,as well as good biocompatibility,which are beneficial for photoacoustic imaging and photothermal imaging/therapy.We also find that the CuCD NSs can realize light-triggered cytosolic and nuclear drug delivery,which significantly enhances the photothermal therapeutic efficiency.2.Synthesis of trace metal-doped carbon-dominated nanoparticles and their application for photothermal therapy（Chapter 3）.In this chapter,a facile one-step,metal salt-involved hydrothermal synthetic route is developed to prepare trace metal（M）-,N-,and O-doped carbon-dominated nanoparticles（termed as MNOCNPs,metal content:<0.1 mol%）with exceptional photothermal properties(e.g.,the ultrahigh extinction coefficient of 32.7 L g^–11 cm^–1).After poly（ethylene glycol）（PEG）conjugation,the obtained nanoagents can simultaneously realize preferable endoplasmic reticulum targeting and specific tumor enrichment.More interestingly,upon laser irradiation,PEG-modified MNOCNPs exhibit considerable nucleolar delivery and increased tumor accumulation.3.Synthesis of platinum-doped carbon nanoparticles（PtCNPs）and their application for cancer cell migration inhibition and multi-organelle-targeted photothermal therapy（Chapter4）.Bare PtCNPs are first prepared by the facile one-step hydrothermal treatment of p-phenylenediamine and potassium tetrachloroplatinate（II）in aqueous solution.After PEGylation,the obtained PEG-PtCNPs can serve as an excellent photothermal nanoagent for cell migration inhibition,laser-triggered nuclear delivery,effective tumor accumulation,and multi-organelle（including mitochondrion,endoplasmic reticulum,lysosome,and Golgi apparatus）-targeted and multimodal imaging-guided photothermal cancer therapy.