Synthesis Of Functionalized Palladium Nanomaterials And Their Anticancer And Antibacterial Applications

Among the noble metals,palladium(Pd),one of the platinum family elements,has drawn much attention because of its high efficiency,stability,and reusability.Recently,many Pd nanomaterials have greatly improved their catalytic efficiency,which makes them indispensible in many other fields,including the biomedical field.In particular,Pd nanosheets(Pd NSs)developed in recent years exhibit unique properties with an atomic thickness.Most notably,their high absorption in the near-infrared region makes them potential in the photothermal treatment of tumors.Moreover,owing to their ultrathin structure,which has less scattering of near-infrared light,the Pd NSs have higher light-to-heat conversion efficiency than other metal nanoparticles with photothermal conversion capability.Besides,the ultrahigh photothermal stability and excellent biocompatibility of the Pd NSs ensure their broad potential for biomedical applications.At present,owing to their intrinsic properties,Pd NSs have developed some applications in biomedical fields such as photoacoustic imaging,tumor targeting,and photothermal therapy,but their present development still faces some challenges.One is the poor stability of clean Pd NSs,which leads to the dependence of further modification for subsequent utilization,and the modification process needs to be simple and effective without affecting the intrinsic function of Pd NSs,and thus it is urgent to develop appropriate modification strategies;another is that current researches only focus on the intrinsic photothermal effect of Pd NSs,and therefore further functionalization is still needed for expanding the potential of Pd NSs in other fields and improving the applicability of Pd NSs in biomedical field.In this thesis,the anticancer and antimicrobial applications of Pd NSs were expanded through specific surface functionalization,and the main results are presented below:(1)First,the Pd NSs were modified with thiol-terminated polyethylene glycol(PEG)to improve their stability under physiological conditions.This modification method is convenient and effective,and achieving the long-term stability of Pd NSs without aggregation while bare Pd NSs cannot be stable overnight.At the same time,as a high atomic number(high-Z)material,the X-ray deposition of ultrathin Pd NSs and the secondary rays producing of Pd NSs after X-ray irradiation can significantly increase the killing efficiency of tumor cells,thus enhancing the effect of radiation therapy.Therefore,this work explored and verified the radiation sensitizing effect of Pd NSs,developing a new metal-based nanoradiosensitizer.Moreover,the palladium element was almost completely excreted from mouse body after 12 days,and no damage to the main organs of mice was observed.Therefore,the safety of Pd NSs enables them to be compared with traditional metal radiotheraputic nanoagents such as gold nanoparticles,silver nanoparticles,and platinum nanoparticles.(2)The sheet-like structure of Pd NSs makes them difficult to be internalized by cells,thereby weakening their anticancer effect.To address this issue,the Pd NSs were modified by the cell-penetrating peptide TAT,and the TAT-modified Pd NSs showed more than 30-fold amount increase in cell retention compared with the Pd NSs without TAT.Meanwhile,imaging results showed that the ingested Pd NSs mainly accumulated in the near-nuclear region.Furthermore,the perinuclear Pd NSs could inhibit cancer cell migration and invasion,while the low-intensity near-infrared laser irradiation significantly improved their inhibitory efficiency.In addition,due to the sensitivity of the nucleus to heat and the increased amount of internalized Pd NSs,the photothermal anticancer efficiency of Pd NSs was greatly elevated under near-infrared laser irradiation.(3)Different from conventional strategies,which realize the stabilization and functionalization of Pd NSs separately,here Pd NSs crosslinked with thiol-terminated four-arm PEG to form an injectable hydrogel via Pd-S bonding,which simultaneously realize the stabilization of the Pd NSs and the facile preparation of a novel photothermal hydrogel.Besides,the introduction of commonly used anticancer drug doxorubicin into the hydrogel resulted in a hydrogel that could be used in the chemo-photothermal combination therapy.Moreover,the doxorubicin-containing hydrogel could maintain a sustained doxorubicin release and the near-infrared laser irradiation could accelerate this drug release process.Therefore,the explosively released doxorubicin and the hyperthermia generated from Pd NSs acted in a synergistic way,achieving almost complete elimination of the subcutaneous solid tumor and inhibition of metastasis after 14 days,which is much better than free doxorubicin or photothermal hydrogel treatment,highlighting the advantages of the combination therapy.(4)The Pd NSs-crosslinked hydrogel was also used for antibacterial application.The hyperthermia generated by the Pd NSs under the near-infrared laser irradiation could kill both Gram-negative and Gram-positive bacteria.Compared with the near-infrared laser irradiation or the hydrogel,which had negligible bacterial toxicity,the irradiated photothermal hydrogel almost completely inhibited the bacterial growth in vitro,and significant antimicrobial and bacterial inhibitory effect were also achieved in vivo.It was revealed that this strategy killed the bacteria by destroying the bacterial cell membranes/walls,without the introduction of antibiotics,which avoids the development of drug resistance.In addition,the hydrogel could prevent the diffusion of Pd NSs and avoid toxicity of the potentially body-retained nanomaterial.In summary,this thesis utilizes surface functionalization to explore or improve the performance of Pd NSs,while maintaining their intrinsic physicochemical properties(especially the efficient photothermal conversion,excellent photothermal stability,and good biosafety),thus achieving excellent anticancer and antibacterial effects through single or combined treatments.With the deepening of the research on Pd and functionalization,it is believed that the Pd-based nanomaterials will play an increasingly important role in more biomedical applications.