Preparation Of Multifunctional Biomimetic And Mineralized Nanomaterials And Their Applications In Cancer Theranostics

Biomineralization is a biologically controlled process by which living organisms produce minerals.Owing to their specific structure and unique properties,biomineralization inspired biomimetic materials are highly attractive in current biomedical research.Meanwhile,in recent years,namomaterials with special tumor targeted capabilities have also drawn more and more attentions for tumor theranostics.However,the potential long-term toxicity toward living organisms hampers their clinical translation.Thus,well-designed biomimetic nanoscale materials may provide new opportunities to the area of nanomedicine.In this thesis,we design several biomimetic nanomaterials and exploit their applications in tumor theranostics.In the first work,we develop a theranostic nano-platform based on polydopamine(PDA)nanoparticles,which then are exploited as a versatile carrier to allow simultaneous loading of indocyanine green(ICG),doxorubicin(DOX)and manganese ions(PDA-ICG-PEG/DOX(Mn)),to enable imaging-guided chemo&photothermal cancer therapy.In this system,ICG acts as a photothermal agent,which shows red-shifted near-infrared(NIR)absorbance and enhanced photostability compared with free ICG.In a mouse tumor model,we achieve a remarkable synergistic therapeutic effect with magnetic resonance(MR)imaging-guided chemo-&photothermal therapy.In the second work,we develop mono-dispersed CaCO3 nanoparticles modified with polyethylene glycol(PEG)as a multifunctional nano-carrier for efficient loading of both Mn2+-chelated chlorin e6(Ce6(Mn))as a photosensitizer,and doxorubicin(DOX)as a chemotherapy drug.The as-synthesized Ce6(Mn)@CaCO3-PEG nanoparticles appear to be highly sensitive to pH and would be rapidly degraded under slightly acidic solutions,leading to efficient release of Ce6(Mn)and thereby significantly enhanced T1-contrast under magnetic resonance(MR)imaging.Beside,DOX release is also pH dependent and shows positive correlation with T1-signal enhancement under MR imaging,allowing real-time monitoring of drug release.Lastly,utilizing such multifunctional biodegradable nanoparticles,we realize a synergistic photodynamic&chemotherapy of cancer in vivo under a precise multimodal-imaging guidance by MR and fluorescence imaging.Based on above two systems,we design a one-pot,dopamine-mediated biomineralized method by a gas diffusion procedure to prepare calcium carbonate-polydopamine(CaCO3-PD A)nanocomposites as a multifunctional theranostic nanoplatform.Because of the high sensitivity of such nanoparticles to pH with efficient degradation under slightly acid environment,the photoactivity of loaded photosensitizer,chlorine e6(Ce6),which is quenched by strong absorption of PDA,is therefore "turned on" with recovered fluorescence and enhanced singlet oxygen generation.In addition,due to the strong affinity between metal ions and PDA,our nanoparticles are able to bind with various metal ions(e.g.,Fe3+,Mn2+,Zn2+ and 99mTc),endowing them multimodal imaging capacities.By utilizing such pH-responsive multifunctional nanocarriers,we can realize a superior in vivo anti-tumor effect by photodynamic therapy(PDT),under a precise guidance of multimodal-imaging.Interestingly,our nanoparticles under normal physiological pH at the quenched status show much lower phototoxicity to normal tissues and thus effectively reduced skin damages under PDT.In general,we design several biomimetic and mineralized nanomaterials and exploit their potential applications in cancer theranostics.Compared with conventional nanomaterials,bio-inspired nanomaterials show excellent biocompatibility,endowing then broad bio-applications with negligible long-term toxicity.Thus,the development of multifunctional biomimetic nanomaterials are promising to be great candidates in cancer theranostics.