Rational Design Of Porphyrin-Based Nanomaterials And Their Biomedical Applications

Photodynamic therapy is a promising method to treat many diseases.The photosensitizer is excited by a laser with a proper wavelength and transfers the energy to the surrounding ground state oxygen to generate singlet oxygen.Singlet oxygen can oxidize biological macromolecules,resulting in cytotoxicity.Porphyrins and their derivatives are a class of compounds with a macrocyclic tetrapyrrole core and different substituents.They are considered to be excellent photosensitizers due to their biocompatibility and good photophysical properties.However,the photodynamic efficiency is often affected by their hydrophobicity.One way to overcome this restriction is through the use of nanotechnology.Here,two types of novel and porphyrin-based nanomaterials are synthesized for photoinactivating bacteria and cancer cells.Specifically,this thesis includes the following two chapters:Porphyrin-based nanoparticles for antibacterial photodynamic therapy:Triaminoguanidinium chloride(TG)is conjugated with meso-tetra(4-carboxyphenyl)porphine(TCPP)by the reaction between carboxyl groups and amino groups.The resultant conjugates can self-assemble during dialysis against water to form nanoparticles(NPs),which are termed TCPP-TG NPs.The synthesis of TCPP-TG NPs increases the aqueous dispersity of TCPP.Compared with TCPP,the TCPP-TG NPs exhibit promoted singlet oxygen generation ability.The experimental results suggest that the positively charged TCPP-TG NPs can rapidly adhere to both Gram-negative and Gram-positive bacteria through electrostatic interaction,which elevates the concentration of photosensitizer around the bacteria and facilitates the diffusion of singlet oxygen into cells within the limited lifetime.Therefore,the TCPP-TG NPs have outstanding antibacterial activity.4 μM and 8 μM TCPP-TG NPs can kill about 99.9999% S.aureus and E.coli under light irradiation,respectively.In addition,TCPP-TG NPs have good stability because their hydrodynamic size and zeta potential values do not change after storage for 4 months.Porphyrin-based metal?organic frameworks(MOFs)for photodynamic therapy: A new bismuth and porphyrin-based metal?organic framework(abbreviated as Bi-TCPP)is solvothermally synthesized using meso-tetra(4-carboxyphenyl)porphine and bismuth nitrate pentahydrate,and its use for photodynamic therapy is tested in vitro.Bi-TCPP is characterized by hydrodynamic size and zeta potential analyses,scanning electron microscopy,and transmission electron microscopy.The results reveal that the Bi-TCPP MOFs are the rectangle-shaped nanosheets.The hydrodynamic size of Bi-TCPP is 343 ± 86 nm.The Bi-TCPP is negatively charged with a zeta potential of ?13.0 ± 4.6 m V.The singlet oxygen generation efficiency of Bi-TCPP is higher than that of TCPP.In vitro anticancer tests confirm that Bi-TCPP achieves an excellent photodynamic anticancer therapeutic outcome.In summary,in this thesis,two types of porphyrin-based nanomaterials for photoinactivating bacteria and cancer cells are designed and synthesized,and their structure and properties are carefully characterized.On one hand,the nanoparticulate form of porphyrin increases its aqueous dispersity and improves its singlet oxygen generation efficiency due to the prevention of its self-aggregation in an aqueous solution.On the other hand,the nanoscale dimension of nanomaterials is beneficial for their interaction with bacteria and cancer cells.Therefore,the two nanomaterials in this thesis show robust photoinactivation efficiency.We hope that this thesis may provide some insights into the future studies about porphyrins and photodynamic therapy.