Constructing And Investigation Of Multifunctional Nanotheranostic Agents For Cancer Imaging And Therapy

Since the concept of theranostic,the integration of diagnostics and therapeutics,was put forward,synthesis and constructing of multifunctional nanotheranostic agents has attracted considerable attention in the field of biomedicine for treating cancer.Recently,with the development of nanotechnology,the use of inorganic nanoparticles for biomedical applications has triggered significant research in imaging,therapy and drug delivery,such as mesoporous silica nanoparticles,Lanthanide-doped upconversion nanoparticles?UCNPs?,emiconductor quantum dots,and magnetic nanoparticles.In this dissertation,we synthesized and constructed two multifunctional nanotheranostic agents,UCNPs and Mn₃O₄ nanoparticles.And we further investigated the feasibility of two nanotheranostic agents for cancer therapy.Specific research results are as follow:1.Lanthanide-doped upconversion nanoparticles?UCNPs?have emerged as excellent candidates for biomedical applications due to enhanced photostability,narrow emission bands,minimized background autofluorescence and low toxicity.The traditional requirement of an excitation wavelength is near 980 nm,which matches the absorption by Yb³⁺ ions?sensitizers?doped into UCNPs.Unfortunately,the 980 nm excitation source is strongly absorbed by water,which caused overheating issues,resulting in significant cell death and tissue damage.Designing and developing novel multifunctional Nd³⁺ doped UCNPs with 808 nm excitation is a promising strategy for addressing these puzzles because of low absorption by water molecules under 808 nm excitation.Due to the high atomic and strong X-ray attenuation,Yb and Nd can be emerged as excellent X-ray computed tomography?CT?contrast agents.As the main composition of melanin,polydopamine?PDA?shows excellent photothermal conversion efficiency and good biocompatibility.Thus,core/satellite nanotheranostic?PDA@UCNPs?was synthesized after UCNPs was modified with polyacrylic aicd?PAA?.The synthesized PDA@UCNPs is theranostic platform for in vivo UCL/CT dual modal imaging-guided photothermal therapy.2.Mn-based nanoparticles with the inherent excellent magnetic properties have regarded as a new class of probes for magnetic resonance imaging?MRI?.Compared with Gd³⁺ agent currently used in clinic,Mn-based nanoparticles have lower toxicity.However,the longitudinal relaxivity of Mn-based nanoparticles reported showed Relatively low.So,design and synthesis of Mn-based T1 MRI contrast agents with high longitudinal relaxivity and low toxicity is necessary.Thus,we designed and synthesized Mn₃O₄@PDA core/shell nanoparticles,which are applied as MR imaging contrasts with ultrahigh longitudinal relaxivity,phtothermal agents and drug carriers for synergetic chemo-/photothermal therapy.Furthermore,the surface of Mn₃O₄@PDA synthesized was modified with the biamino polyethylene glycol?NH₂-PEG-NH₂?for further conjugation with folic acid?FA?,which can be improve the stability,biocompatibility and the ability to target tumor.The synthesized FA-Mn₃O₄@PDA@PEG nanocomposites are regarded as nanotheranostic agents for MR imaging guided synergetic chemo-/photothermal therapy.