Co-Assembly Of Porphyrin For Dual-Modal Imaging Guided Photodynamic Therapy

The challenges of high morbidity,infiltrative growth and low therapy efficiency were the key killer for human's health.Surgery,chemotherapy and radiation therapy were three major common therapy means of cancer therapy.However,surgical treatment was hard to excise completely,resulting in recurrence of cancer.Unfortunately,the radiotherapy and chemotherapy were non-selective therapy with high systemic toxicities.Moreover,the lack of in vivo real-time monitoring the therapy progress also limit them to be an unsatisfactory therapy mean.Therefore,there has an urgent need to develop efficient and safe theranostic method for cancer theranostic.Photodynamic therapy(PDT),a safe and noninvasive green therapy method of cancer,possess some merits of safe,low toxicity and damage,good selectivity and low tumor tolerance,which would generate singlet oxygen(1O2)damaging the cancer cells upon the existence of photosensitizer,tissue oxygen and controllable irradiation.The theranostic efficacy of photosensitizer and target manner were two key of PDT.Thus the fabrication of efficient targeted photosensitizer with multi-modal imaging functions for visual diagnosis and treatment of cancer was the major problem in the field.Porphyrin was an ideal photosensitizer with rigid macrocyclic structure,high symmetry,large molar extinction coefficient and high yield of singlet oxygen upon irradiation for PDT.However,most of porphyrin photosensitizers are too hydrophobic to utilized for effective retention in tumor sites.Self-assembly,particularly co-assembly,is a highly effective method to prepare of hydrophilic porphyrin nanomaterials,which show huge potential in biological theranostic field of porphyrin assemblies with abundant morphologies and multiple functions by the parameter adjustment of assembled manner and building blocks,etc.However,the mutual interference of assembled units in multi-component and multifunctional porphyrin nanosized coassemblies,the strict reaction parameters,such as components,ratio and assembly environment.There it still a huge challenge for controlled preparation of multifunctional nanoassemblies via co-assembly.In this work,we design a multi-component and multifunctional co-assembly method.Typically,we rationally select functional assembled units and adjust the assembled microenvironment via microemulsion assisted mesophase transfer co-assembly method to fabricate the porphyrin coassemblies with magnetic resonance imaging/fluorescence dual modal imaging(MRI/FLI)guided PDT for cancer theranosticapplication.In detail,this work,Gd(III)meso-tetraphenyl porphine 2,4-pentane dionate(Gd TPP)with MRI function and Zinc meso-tetraphenyl porphine(Zn TPP)photosensitizer were selected as units to coassemble for the negative Gd TPP/Zn TPP nanocomposite(GZNs)with 64.0 nm of diameter.Furthermore,homologous target modification were used to coat onto the GZNs for enhanced target function.Benefited from the above operation,this work achieve the following aims,(i)firstly,we achieve the enhanced coassembly by the advantages of same rigid macrocyclic structure and high symmetry from two porphyrin units,which promote the homogeneous distribution of functional units.Simutaneously,the disorder degree of aggregated units and yield of product was improved.(ii)Besides the increased yield,the coassemblies also achieve the function combination of MRI/FL dual modal imaging and 1O2 generation upon irradiation from two metalporphyrin,i.e.1+1>2 integration.(iii)To improve the retention and therapy efficiency,the nanosphere was used biomimetic target modification,i.e.,homologous target cancer cell membrane,to improve the biocompatibility and targeted specificity efficiency.The modified nanotheranostic achieve excellent dual modal imaging guided efficient PDT efficacy(80.6%).