Dissertation > Medicine, health > Basic Medical > Medical science in general > Biomedical Engineering > General issues > Biomaterial

Evaluation of Micro/nano Near-Infrared Photoabsorbers for Visible Photothermal Therapy

Author ChaZhengBao
Tutor DaiZhiFei
School Harbin Institute of Technology
Course Biomedical Engineering
Keywords copper sulfide polypyrrole photothermal therapy ultrasound imaging photoacoustic tomography
CLC R318.08
Type PhD thesis
Year 2013
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Photothermal therapy (PTT) has gained popularity as a promising minimallyinvasive alternative to surgery by delivering photoenergy directly into tumor tissueswithout causing systemic effects. However, PTT agents are required for realizingeffective PTT. Currently, inorganic PTT agents with high photothermal conversionefficiency, have difficulties in surface modification, targeting and carrying drugs.And their non-biodegradability is still worrying. Organic PTT agents have goodbiocompatibility but the low photo-thermal conversion efficiency, photothermalstability and complicated synthesis process limit their further use. On the other hand,appropriate imaging techniques are essential to realize successful PTT treatment.Thus, introducing imaging modalities to PTT agents with high targeting and drugloading ability, high photothermal conversion efficiency and photothermal stabilityas well as simple preparation method, is of great importance.CuS nanoparticles (NPs) have difficulties in targeting and drug loading. In thisstudy, a novel microbubble system was developed for both ultrasound imaging andtargeted CuS NPs delivery using ultrasound-targeted microbubble destruction to killtumor cells by PTT. Futhermore, multifunctional CuS NPs stabilized with DOX-conjugated gelatin (CuS@Gel/DOX NPs) were developed to combine thephotoacoustic tomography (PAT), enzyme-responsive drug delivery and PTT forcancer treatments. CuS@Gel/DOX NPs could selectively release drug due to theenzymatic degradation of gelatin-DOX conjugates. Moreover, a synergistic effect inkilling cancer cells was found by the combined photothermal therapy andchemotherapy with minimal side effects.In order to avoid the potential long-term toxicity of inorganic photothermalagents, uniform biocompatible polypyrrole (PPy) NPs with a average diameter of~46nm were constructed from a facile one-step aqueous dispersion polymerizationmethod. The as-prepared PPy NPs exhibited good colloidal stability, significantphotothermal conversion efficiency due to strong NIR absorption and goodphotostability, higher than the well known Au nanorods. Moreover, the strong NIRabsorption allowed visualization of PPy NPs-containing agar gel embeded in chickenbreast muscle at a depth of~4.3cm by PAT. Our results indicate that PPy NPs arepromising agents both for PAT and PTT, with good biocompatibility.To overcome the inferior solubility of polypyrrole materials in common solvents,soluble PPy complex were synthesized and used for developing PPymicro/nanocapsules with encapsulated perfluorooctylbromide (PPyPFOBMC/PPyPFOBNC) from a facile one-step emulsion method. Owing to the encapsulated liquid PFOB and strong NIR absorption of PPy shell, the resulted PPyPFOBMC/PPyPFOBNC not only provided excellent contrast enhancement for ultrasoundimaging, but also served as efficient photoabsorbers for NIR photothermal tumorablation using a rather lower laser power density at0.64W/cm2. In vitro and in vivostudies both showed no side effects of PPyPFOBMC/PPyPFOBNC was observed atour tested doses. Thus, this simple and highly efficient theranostic agent based onpolypyrrole-composites would remarkably improve the methodologies for cancerdiagnosis and therapy.Simple physical combination of different dianostic and therapeutic elementwould give a relatively high onetime dose which may cause systemic toxicity andimpose an extra burden for the patients to excrete the theranostic agents. Thus,organic polypyrrole hollow microspheres (PPyHM) with good dispersity weredeveloped for the first time as an photothermal agent with US-responsive capabilityvia a facile oil-in-water (O/W) micro-emulsion method by employing soluble PPycomplex. Due to the π-π interaction of PPy complex and polyvinylpyrrolidone, thegenerated PPyHM not only provided excellent contrast enhancement for ultrasoundimaging, but also served as efficient photoabsorbers for NIR photothermal tumorablation both in vitro and in vivo.In conclusion, novel microbubble with CuS NPs could be used for bothultrasound imaging and targeted CuS nanoparticles (NPs) delivery through UTMD tokill tumor cells by PTT; CuS@Gel/DOX NPs could selectively release drug due tothe enzymatic degradation of gelatin-DOX conjugates as well as strong NIRabsorption for PAT and PTT; Organic PPy NPs are promising agents both for PAT andPTT, with good biocompatibility; PPy composites fabricated from soluble PPycomplex not only provided excellent contrast enhancement for ultrasound imaging,but also served as efficient photoabsorbers for NIR photothermal tumor ablation bothin vitro and in vivo.

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