Nanoaggregates Based On Amphiphilic Near-infrared Dyes And Their Application In Biomaterials

Functional dyes with near-infrared(NIR)absorbing properties exhibit remarkable optical properties,tunable chemical structure and good biocompatibility.In addition,the dyes assemblies constructed by functional dyes molecules with photoabsorption and photoemission properties,have potential application in important biomedical research fields,such as biological detection,biological imaging,photodynamic therapy and photothermal therapy.The related study has become a multi-disciplinary cross research hotspot.In this thesis,a series of novel NIR amphiphilic dyes molecules are designed and synthesized,and the biological properties of the nanoaggregates are studied and characterized.The specific research contents are as follows:1.A series of amphiphilic aza-BODIPY 1a-c and 2a-c bearing different length of hydrophilic chains are synthesized according to Cu^I-catalyzed“Click”reaction,and their chemical structures are characterized by ¹H NMR,¹³C NMR,high resolution mass spectrometer(HRMS)UV-Vis absorption spectroscopy and fluorescence spectroscopy.2.The nanoaggregates based on amphiphilic aza-BODIPY 1a-b and 2a-c are prepared,and their aggregation behavior are studied through UV-Vis absorption spectroscopy.The experimental results indicated that the aza-BODIPY 1a-b and 2b formed two types of aggregates in H₂O,i.e.kinetically controlled Agg.I and thermodynamically stable Agg.II.Compared with monomeric molecule,Agg.I show red-shifted and broaden absorption and Agg.II is equipped with red-shift,extremely narrow absorption band,and high molar absorption coefficient,which indicating the formation of J-type aggregates;the morphology of aggregates is characterized by transmission electron microscopy(TEM)and atomic force microscopy(AFM).Agg.I show spherical morphology with diameter of c.a.20–60 nm,and morphology of Agg.II is fibrous structure with a diameter of?10 nm and hundreds of nanometers in length.Different from 1a-b and 2b,only one phase state is observed in aggregation behavior of 2a and 2c,and their absorption spectra and morphology is similar to Agg.II and Agg.I,respectively.3.The nanoaggregates based on aza-BODIPY 1a has been studied as a nano-biomaterial.The fibrous 1-NFs(Agg.II)with long blood circulation can be transformed into spherical nanoparticles 1-NPs(1a-Agg.I)with increased temperature triggered by ear-infrared(NIR),which are conducive to increasing the penetration in the solid tumor.Second,through 655 nm laser irradiation,the intrinsic photothermal effect of 1-NFs causes a local temperature increase to?48°C,realizing the transformation of 1-NFs to1-NPs.The in situ morphological transformation is real-time detected by photoacoustic(PA)imaging.By monitoring the change of the PA signal at a specific wavelength,the in vivo deformation process of nanomaterials can be traced.Consequently,the in situ morphology transformation of 1-NFs can simultaneously realize long blood circulation and deep penetration,resulting in the enhanced antitumor outcome.In contrast,fibrous nanoaggregates 2a-Agg.II based on aza-BODIPY 2a,named as 2-NFs,can not realize in situ phase transitions to increase the penetration of solid tumors,so its anti-tumor effect is not as ideal as that of 1-NFs.4.The biphasic transition of aza-BODIPY-based nanoaggregates is reasearched for temperature controlled photothermal therapy.First of all,Agg.II of 1a and 1b(1a-Agg.II and 1b-Agg.II)exhibit red-shift and extremely narrow absorption band in NIR spectral range(799 nm),which can give rise to NIR laser induced photothermal heating.The photothermal conversion efficiency of 1a-Agg.II and 1b-Agg.II is 37.2%and32.4%respectively.The phase transformation of 1a-Agg.II and 1b-Agg.II can be realized through regulating the laser power density.The phase transformation of aggregates can stabilize the system for the reduced absorption of NIR laser,thus realizing self-regulation of temperature in photothermal therapy.Next,the phase transition temperature of 1a-Agg.II and 1b-Agg.II is 48.5 ^oC and 58.6 ^oC,which can be regulated by adjusting hydrophilic chain length of aza-BODIPY molecule.The phase transformation of 1a-Agg.II and 1b-Agg.II can be detected by monitoring photoacoustic(PA)signals at specific wavelength.The phase transformation regulated through NIR laser can realize the temperature controlled photothermal therapy.