Functional-Protein-Assisted Fabrication Of Fe-Gallic Acid Coordination Polymer Nanonetworks For Localized Photothermal Therapy

?Objective?Traditional cancer treatments,such as radiotherapy and chemotherapy,have been widely applied for clinical cancer therapy,but they suffer from the risk of side effects such as destroying the immune system and increasing the incidence of cancer recurrence.Photothermal therapy?PTT?is emerging as an alternative method for cancer therapy in recent years.Meanwhile,with the continuous innovation of nanotechnology,many nanoparticles for photothermal therapy have been developed,among which coordination polymer nano-materials?MOF?as a universal nano-platform show great potential in a variety of biomedical applications.In order to obtain photothermal nanomaterials with better biocompatiblity and various biofunctions,we showed functional-protein-assisted fabrication of Fe-GA nanonetworks?BSA-Fe-GA,OVA-Fe-GA,HSA-Fe-GA?via biomineralization for localized photothermal therapy.?Methods?Taking Bovine serum albumin?BSA?as template,Fe³⁺as metal center,and gallic acid extracted from plants as organic ligand,BSA-Fe-GA coordination polymers were synthesized via mild biomineralization in a mild alkaline solution.Analogously,we extended this synthesis method to the other two proteins,ovalbumin?OVA?and human serum albumin?HSA?,to synthesize OVA-Fe-GA and HSA-Fe-GA.The purified protein-Fe-GA were then characterized systematically.Cytotoxicity and phagocytosis of protein-Fe-GA were investigated by cellular MTT assay and ICP-AES,respectively.The photothermal property of BSA-Fe-GA nanonetworks was assessed by photothermal heating experiment and photothermal tumor ablation in vitro and in vivo.Flow cytometry and ELISA cytokines quantitation were used to analyze whether the OVA immune activity in the OVA-Fe-GA nanonetworks was affected by the synthesis process.?Results?Mild alkaline condition permitted the formation of Fe-GA nanonetworks with favorable near infrared?NIR?absorbance and impressive photothermal performance.Good biocompatibility and excellent photothermal effect in vitro and in vivo ensure the photothermal tumor ablation of BSA-Fe-GA nanonetworks.Similarly,both HSA and OVA were designed to self-assemble into protein-Fe-GA coordination polymer nanonetworks with excellent photothermal effects.Moreover,the proposed OVA-Fe-GA nanonetworks successfully induced the maturation of dendritic cells?DC2.4?and macrophage cells?RAW264.7?.The immune activity of OVA in OVA-Fe-GA nanonetworks was retained efficiently via the mild synthesis approach.?Conclusions?In this work,the precursors selected for synthesis are low-toxicity,the synthesis procedures are simple and easy to repeat,the products are highly biocompatible with excellent photothermal effect,and the obtained BSA-Fe-GA nanonetworks were successfully used for photothermal tumor ablation.We further fused various bioactive proteins into Fe-GA coordination polymers,in which the immune activity of OVA was fully demonstrated.This mild synthesis method provides a feasible solution for the design and development of nanomaterials based on coordination polymers including photothermal reagents,multi-functional nanovaccines and various biological application materials.