Application Of Conjugated Polymer As A Therapeutic Platform In Treating Diseases

Researches at the interface of biological and medical sciences have given rise to polymer-based pharmaceuticals.Polymer therapeutics include macromolecular drugs,polymer-protein conjugates,drug-loaded polymer micelles,and polyplexes for DNA delivery.Although the most useful platform to study biomedical science remains to be biomacromolecules,speaking on behalf of the material versatility of man-made polymers in terms of their molecular weight,polydispersity,reactivity,and synthetic diversity,a polymer approach to vesicles would seem to offer many possibilities.Among all these polymers,conjugated polymers(CPs)draw great attention because of the excellent optoelectric properties,which can be applied in biological and material sciences.In this thesis,we demonstrate the applications of the conjugated polymers in diseases treating.Aiming at different characters of different diseases,different drug delivery systems were organized and treating efficacy were studied.The whole topic was divided into four sections:1.A negative feedback control circuit was designed to suspress the activity of lipase,according to the characteristics of the enzyme.A daily meal intake was mimicked to further study the enzyme inhibition.2.The negative feedback circuit was applied to treat obesity,and treating efficacy was investigated.3.Conjugated polymer was utilized to treat cancer as a ROS inducer.Treating efficiency was also discussed.The main contents are listed below:1.To facilitate the application of conjugated polymers in in vivo imaging,5,7-bis(5-bromo-2-thienyl)-2,3-dimethyl-thieno[3,4-b]pyrazine was added to alter the energy band of polyfluorene,whose emission peak was red-shifted to near-infrared region.Polycaprolactone was added to the side chain by a ring opening polymerization to achieve the function of hydrophoby and lipase-cleavable side chain.The nanoparticles(NPs)were prepared by self-assembly of amphiphilic copolymer BTTPFN-g-PCL.Lipase-responsiveness was examined in buffers,which simulate the condition in stomach and intestine,respectively.Furthermore,varied lipase concentrations were applied to study the release behavior,or rather negative feedback regulation of the nanocarrier.We then assessed the release kinetics of orlistat in response to cyclically varied lipase level.2.High fat diet was performed to induce diet induced obesity in male ICR mice.The drug delivery system was given to diet induced obesity mice by oral gavage.And the non-invasive fluorescence images express the biodistribution and excretion profiles of the NPs.After the administration,fluorescence signals were observed throughout the body,suggesting that the nanocarrier had been absorbed and delivered through blood circulation.So we further studied the transportation of the NPs across the intestine,which finally showed that nanocarrier,as well as lipase,could help imrprove the oral bioavailability of lipase-inhibitor.After single administration of the nanocarrier with encapsulated orlistat,change of body weight percentages was kept for comparison.Then we assessed the therapeutic efficacy of the daily-administrated NPs.Body mass index and weight of liver and fat pads were compared to verify the weight loss effect.Finally,oil red O stained liver and serum parameters were examed to ensure the healthy status.3.The success synthesis of PFBTA extended the absorption and the fluorescence spectra to a wavelength large than 700 nm,which is considered suitable for deep tissue penetration.Moreover,the conjugated backbones exhibit sensitivity to oxidative stress.The conjugated structure was utilized to test whether the ROS concentration was high enough to cause damage to cellular components.Our results indicated that the differentiation in fluorescent spectra of CPs before and after getting oxidized can be used to evaluate the oxidative stress in vivo.To eliminate the unexpected influence on normal tissues,m-dextran was added to provide the character of pH responsive.When irradiated,apoptosis of cancer cells could be observed.Similar results were detected in tumor tissues after treatment with TUNEL staining assay.Amazingly,tumour-bearing mice with day-light treatment show as good outcomes as DOX-treated mice.