Preparation and Biomedical Applications of Porphyrin-Based Porous Nanocomposites

Author:Zheng Xiao Hua

Supervisor:xie zhi gang


Degree Year:2019





As one of the most widely studied photoactive materials for phototherapy,porphyrin-based photosensitizers possess favorable biocompatibility and facile chemical modification.However,the intrinsic large π bond conjugated and hydrophobicity properties of the porphyrin structures lead to the aggregation and precipitation,thus limiting their accumulation in tumor sites,which ultimately weakened the phototherapy effect.The rational design of biocompatible and biodegradable nanocarriers is an efficient alternative to overcome these "Achilles’heels".Metal-organic frameworks(MOFs)and porous organic polymers(POPs),as new types of carrier materials with great potential due to the periodic order of structures,the richness of surface porosity and favorable biocompatibility,have been utilized in the field of cancer therapy and bioimaging.To overcome the aggregation and quenching induced poor solubility and low photon utilization efficiency of porphyrins,the research synthesized a series of novel porphyrin-based nanoporous composites and nanoarchiectures to significantly improve the dispersion and photochemical properties of the porphyrin-carrier systems.And we clarified the relationship between the spatial arrangement of PSs molecules in the porous materials and the phototherapy activity.We further explored the enhancement effect of interface between different types of porous materials on the photoactivity of porphyrin-based composites.In a series of studies,we successfully applied these systems to tumor phototherapy and related photothermal,photoacoustic and CT imaging.The primary research results include the following aspects:(1)A self-template synthesis approach has been applied to the design and preparation of photoactive MOF@POP nanocomposites.The size distribution and morphology of such core-shell nanoparticles could be simply controlled by tuning the amine sites on the outer surface of selected UiO-AM seeds and the feeding ratios of H2P and terephthalaldehyde.After POP chemical modification,the high crystallization,pore integrity,and well-dispersed size distribution of UNM nanoparticles maintain well as UiO-AM itself.Importantly,the above light-activated system could be easily endocytosed by cancer cells,thus enabling to efficiently generate singlet oxygen to induce apoptosis of cancer cells under light illumination.(2)A facile mixed-component strategy has been utilized to incorporate photoactive chlorin into the Hf-UiO-66 archetype structure without altering the underlying topology.Such TCPC-UiO possesses high photostability,good biocompatibility,and an efficient photodynamic and photothermal therapy effect regulated by the spatial arrangement of TCPC ligands.In addition,Hf clusters could largely enhance the phototherapy performance under laser irradiation via the heavy atom effect,and also endow TCPC-UiO with a CT imaging function.Favorable photothermal conversion efficiency facilitates the subsequent application of TCPC-UiO in photoacoustic imaging and PTT.In vivo experiments demonstrate that as-synthesized TCPC-UiO exerts an obvious antitumor effect against H22 tumor-bearing mice with a tumor inhibition as high as 90%.(3)We have rationally developed a multifunctional HUC-PEG nanocomposite with a facile integration of non-photoactive Hf-UiO-AM MOFs and chlorin-based POPs for the favorable photo-trigged therapeutic system.The increased extinction coefficient of chlorin compared to porphyrin at the lowest-energy Q band highly elevated the light-harvesting ability and also propagated the generation both ROS and heat,thus facilitating superior antitumor activity.Comparing with classical photodynamic porphyrins-contained MOF and COF and our selected controls,the interface effect between the heavy atom effect of Hf in non-photoactive Hf-UiO-AM and TAPC in POPs simultaneous enhanced both photodynamic and photothermal performances of obtained HUC-PEG nanocomposite to realize a "0+1>1" effect.The so higher light-heat conversion at 41%endowed the current system with the photothermal imaging function.Furthermore,HUC-PEG exhibit remarkable physiological stability and favorable biocompatibility after the introduction of PEG.The good antitumor activity in the following in vivo phototherapy could be observed.(4)We firstly synthesized the disulfide-connected chlorin dimers using a covalent coupling method and then,prepared their corresponding nanoparticles by a self-assembly approach.The as-prepared chlorin dimers NPs are robust and stable in aqueous media,possessing highly effective ability of absorbing light energy.The absorbing light could be transformed into singlet oxygen and heat energy for PDT and PPT,respectively.The combination of PDT and PPT could effectively inhibit the growth of tumor in in vivo study.In addition,the chlorin dimers NPs also possess the ability of photothermal/PA imaging,which can be used for guiding and monitoring the tumor treatment.