Preparation And Photoresponse Properties Research Of Silica-based Composite Powders Loaded With Methylene Blue

Methylene blue(MB)is a near-infrared dye approved by the US Food and Drug Administration(FDA)for clinical applications of surgical imaging and photodynamic therapy.Its advantages include short period of photosensitivity,high sensitivity,and unability to cause drug resistance in cancer.The aggregation of MB monomers to dimers and trimers will cause the alternation of the type II photochemical reaction pathway to the type I pathway,the reduction in the efficiency of photodynamic therapy and the proneness to fluorescence quenching.The clinical applications of MB molecules are greatly limited by these obstacles,which can be significantly improved through loading of MB molecules in drug vehicles to modulate their aggregation states and invesitagate their photoresponse properties.Herein,the modified St?ber method was firstly employed to prepare MB-loaded silica particles(silica-MB),and then,reaction conditions and coating processes were varied to prepare composite powders with different shell structures.The aggregation states of MB were modified and their photoresponse properties were investigated in detail.The main conclusions were drawn as follows:(1)Performance of the type ? of photochemical reaction pathyway of methylene blueAntisolvent crystallization is employed to coat methlyene blue(MB)-loaded silica by shellac precipitation(silica-MB@shellac).The encapsulation of shellac shell on silica-MB modulates the aggregation state of MB,which endows silica-MB@shellac a decreased MB's thermal stability,enhanced photoluminescence intensity,improved stability against in vitro reduction by ascorbic acid and retained photodynamic therapy activity.From the absorbance of MB supernatant obtained during incubation,the concentrations of MB monomers and dimers are determined via a non-linear regression analysis to investigate the influence of shellac coating on MB's release mechanisms from silica-MB@shellac.According to the simulated models,small diffusion constants of MB are caused by limited diffusion through shellac shells with high compaction degrees.These are observed for samples synthesized under high supersaturation degree during antisolvent crystallization.High degree of supersaturation is achieved through increasing shellac concentration,additive amount and dropping rate of antisolvent,as well as decreasing p H values of aqueous buffers as antisolvent.Furthermore,a combined mechanism of Fickian diffusion and Case-I? relaxation is proposed to describethe release behaviors of MB monomer and dimers from silica-MB@shellac.Therefore,this work may shed light on the encapsulation method of polymer on drug-loaded powders and the control of aggregation states of photosensitizers to promote the photoluminescence intensity,photodynamic therapy efficiency and controlled release behaviors.(2)Performance of the type ? of photochemical reaction photoway of methylene blue.Firstly,silica-MB particles were prepared with a modified St?ber method.Core-shell structured silica-MB@SHPBS composite powders were then fabricated after encapsulation of shella film prepared through antisolvent crystallization with phosphate buffered saline as antisolvent.After heat treatment at 90?180oC,MB molecules in these carriers were finally aggregated to dimers and trimers.The compaction densities of shellac films became high as a result of heat treatment,which caused high thermal stability of MB,shift of Raman peaks and reduction of quantum yield of photoluminescence.The compacted shellac films limited the outward diffusion of MB,which endowed MB molecules release behaviors with sustained,controlled and p H-sensitized characteristics in buffer solutions.In solutions with low oxygen concentrations,MB dimers and tirmes were involved in the type I photochemical pathway and gerated radical groups,which were crucial for photodynamic therapy in hypoxic environments of solid tumor issues.(3)Preparation and fluorescence performance of silica-MB@Am C composite powdersAs a kind of near-infrared dye,methylene blue(MB)molecule is proneness to form excimers in solid powder or solution at high concentration,which results in weak photoluminescence intensity during clinic diagnostic and cell labeling applications.Aiming to improve the quantum yield of MB,silica-MB particles are herein prepared and treated hydrothermally(HT)to synthesize silica-MB-HT and silica-MB@amorphous carbon with glucose as carbon source(silica-MB@Am C).Significantly,hydrothermal treatment causes destruction of Si-O-Si network,modulation of aggregation state,variations of energy gap and release behavior of MB.In comparison with that of silica-MB,emission intensities of both silica-MB-HT and silica-MB@Am C increase greatly and their photoluminescence peaks are blue-shifted,which are closely related with Raman-active vibration modes of MB in a locally-excited state.Enhanced emissions of both silica-MB-HT120 and silica-MB@Am C120 are observed with increased intensities of Raman peaks assigned to in-plane bendingvibrations of C-H bond during skeletal deformation of C-C in ring.In contrast,the in-plane bending vibration for C-H bonds at end group of MB is considered as a way of radiation decay,and strong vibration of this Raman-active mode causes weak emission intensities of silica-MB-HT180 and silica-MB@Am C160.The stabilities of photophysical properties are compared after 72 h of incubation in buffered mediums or 5h of illumination under ultraviolet light.The photoluminescence intensity of silica-MB@Am C120 fluorophore increase remarkably after illumination,meeting the requirements of reduced photobleaching,minized solvatochromic shift and increased fluorescent efficiency during versatile applications.