Study On Fluorescence/X-ray Functionalized Highly Branched Aliphatic Polyesters

Bioimaging technology is developing rapidly due to its non-invasive,visualization,high-sensitivity,as well as its advantages in diagnosis and personalized therapy of intractable diseases in real-time and in-situ in the clinic or post-surgical medical devices follow-up.In particular,the innovative bioimaging platforms combining biomaterials and contrast agents(CAs)have exhibited the promising prospects in the medical applications because it has the advantages of adjustable composition and specific targeted recognition.Among them,aliphatic polyesters(such as PLA,PCL,etc.)have attracted more attentions due to their excellent biodegradable,biocompatibility and physical mechanical properties.However,they show the inherent shortcomings of chemical and bioinert character without functional sites along the polymer backbone.To introduce more functionalized sites and tailor the properties of polyesters,highly branched structures are performed.Therefore,it is of great importance in potential application to develop a well-defined highly branched multi-functionalized polyesters with tailored functionality and performance for the integrated diagnostic and therapeutic platforms combining the bioimaging and drug therapy.A series of linear-comb/star-comb fluorescent and fluorescence/X-ray bifunctionalized poly(L-lactide)and poly(?-caprolactone)(PLLA/PCL-COU or PLLA-COU-I)were synthesized by direct initiation or post-functionalization methods using fluorescent initiator or linear/star hydroxylated polybutadiene as macroinitiator,respectively.Coumarin and triiodobenzoic acid were separately selected as model fluorescent and X-ray contrast agent.The effect of different chemical structures,architectures,degree of branching(DBs)and end-group on the thermal and photophysical properties,as well as the in vitro drug release and enzymatic degradation performance were studied systematically.The fluorescence and X-ray imaging effects as well as biocompatibility were also evaluated.The main content are as follows:1)A facile end-functionalization method using hydroxylated coumarin as fluorescent initiator to synthesis four kinds of fluorescent biodegradable aliphatic polyesters(PLLA/PCL/PCL/PTMC-COU).The dependence of fluorescence properties and in vitro drug release on chemical structures were investigated.The results show that the difference in electron with-drawing effect and the density of ester groups are responsible for the changes in the fluorescence quantum yield.During in vitro drug release,the release rate of PCL-COU microspheres is dramatically faster than that of PLLA-COU microspheres due to the differences of the materials nature and their surface morphology.Fluorescent polyesters microspheres can retain the fluorescence properties and emit bright blue light for fluorescence tracing during the degradation process.2)A series of well-defined and multi-functional linear-comb/star-comb fluorescent poly(L-lactide)s(lc/sc-PLLA-COU)were synthesized using linear/star hydroxylated polybutadiene as macroinitiator via ring-opening polymerization and DCC dehydration condensation reaction with coumarin containing carboxyl group as fluorescent agent.The influence of different architectures,DBs and end groups on their fluorescence properties,in vitro drug release and enzymatic degradation behaviors were analyzed systematically.It can be founded that the fluorescence properties of PLLA-COU depend on the degree of branching.The ? in dilute solution is the result of the "steric shielding effect" and "intramolecular quenching effect",whereas ? in solid state or concentrated solution is related to intra-/inter-molecular quenching.The in vitro drug release rate and water degradation of lc-/sc-PLLA-COU-PTX is dramatically accelerated because of their decreased crystallinity and looser packing.The enzymatic degradation of PLLA-COU more depends on DB and end-group number and changes from surface erosion to bulk erosion.PLLA-COU always emit bright blue fluorescence and exhibit bioimaging properties.3)A series of well-defined and multi-functional linear-comb/star-comb fluorescent poly(?-caprolactone)s(lc/sc-PCL-COU)were synthesized using linear/star hydroxylated polybutadiene as macroinitiator via ring-opening polymerization and DCC dehydration condensation reaction with coumarin containing carboxyl group as fluorescent agent.The relationship between the architecture and properties was explored comprehensively.It is concluded that the crystallinity of PCL is significantly decreased with the DBs increasing and coumarin introduced,which is attributed to the increase of steric hindrance and crystal defects.Owing to the difference in the flexibility of the polyester chains,the ? of PCL-COU is slightly lower than that of PLLA-COU.The dependence of drug release and enzymatic degradation of PLLA/PCL-COU on the architectures and DBs behave differently,which stems from the more obvious restricted movement of PCL-COU branching chain by the core during crystallization.4)A series of well-defined and fluorescent/X-ray bifunctionalized linear-comb/star-comb poly(L-lactide)s(l-/s-lc-PLLA-COU-I)were synthesized using linear hydroxylated polybutadiene as macroinitiator via "one pot" method of ring-opening polymerization.And coumarin and triiodobenzoic acid as fluorescent and X-ray contrast agents were reacted by DCC dehydration condensation reaction based on the "one pot".The regulation method of coumarin and iodine of PLLA-COU-I and impacts of the TIBA introduction on the properties were investigated,and the fluorescence and X-ray imaging effect were also evaluated.It can be found that for the PLLA-COU-I with the lower DB,the introduction of TIBA decrease ?,and the reduction amplitude decreases accordingly as the TIBA increasing,while the ? of PLLA-COU-I with higher DB increases and the amplification also increase then keep stable.The enzymatic degradation rate of 1-/s-/lc-PLLA-COU-I is in the order of star>linear>linear-comb,because the introduction of TIBA changes the compatibility of end groups with PLLA matrix.Moreover,PLLA-COU-I emits bright blue fluorescence and excellent X-ray effects,and has good biocompatibility.In conclusion,the highly branched multi-functionalized polyesters have a great potential as an integrated diagnostic and therapeutic biodegradable drug delivery system that combines dual functions of fluorescence/X-ray bioimaging and drug therapy.