Constructio And Application Of Novel Low-Dimensional And Efficient Intelligent Responsive Biomaterials

The wide application of nanotechnology in the field of biology has promoted the development of nano biotechnology,in which nano-drug carrier is the most attractive research area.So far the most common method used to fabricate nano-drug carriers is self-assembly method,which as a bottom-up synthesis method has been widely used to fabricate functional materials with unique optical,magnetic,electric,catalytic and biological properties.In this thesis,a series of novel nano-drug carriers is prepared by self-assembly between biocompatible polymers and post-modified polymers.The properties of the prepared carriers,including size,solubility and fluorescence intensity,etc.,can be adjusted by changing the reaction conditions or the polymer molecular weight.The carriers are applied in life analysis,biological imaging and detection of low-concentration substances.This thesis mainly contains three parts listed as below:(1)Covalent organic frameworks(COFs)have the huge potential appilications in drug-delivery carriers because of their superior biocompatibility and structural versatility.However,COFs-based drug delivery systems are still in a nascent stage.Especially,the exploration of COFs in vivo studies has not been reported yet.To tackle these everlasting challenges,we,for the first time,develop a series of water-dispersible polymer-COF nanocomposites(PEG-CCM@COF-1)through an elegant self-assembly approach that combines the COF carrier and polymer modification in one pot,and further study on their drug delivery behaviors in vitro and in ivivo.The results show that the composite adopts a micelle-like structure in which COF-1 serves as the hydrophobic core,the PEG in the amphiphilic polymers(PEG-CCM)as the hydrophilic part,and the end CCM(CCM)as hydrophobic tail to trap the anti-cancer drug,doxorubicin(DOX),which can also penetrate into APTES-COF-1 channels at the same time.Inside the cell,once PEG-CCM is unplugged,DOX is spontaneously released.Remarkably,the self-assembled carrier(PEG-CCM@COF-1)exhibits strong fluorescence in both solid state and solution,whose real-time fluorescence response is utilized to track COF-based composite upon cellular uptake and DOX release.Fluorescent tracer experiment indicates that PEG-CCM@COF-1 accumulates efficiently in tumors after intravenous injection.Compared with the free DOX formulation,DOX-loaded PEG-CCM@COF-1 nanocarrier shows an enhanced tumor-inhibition effect.Taken together,our study showcases a novel synthesis of water-dispersible PEG-CCM@COF-1 nanocomposites as smart carriers for drug delivery with remarkable anti-cancer therapeutic efficiency.As far as we know,this represents the first study pertaining to a facile methodology to prepare monofunctional PEG-CCM@COF drug-delivery nanocarriers for therapeutic applications.More intriguingly,the nano drug carrier PEG350-CCM@APTES-COF-1 can go into the brain,and its specific role in brain targeting study has been elucidated.Further studies are under way.(2)The combination of photothermal therapy and photodynamic therapy(PTT/PDT)offers unique advantages over individual PDT.In order to improve the safety and therapeutic efficacy,we design a novel cost-effective therapeutic strategy for simultaneous synergistic PDT/PTT treatment.Nanofibers are firstly formed through self-assembly of chitosan(CS)and iron oxide nanoparticles(IONPs).The amino groups on the surface of CS are then used to bond with the terminal carboxyl groups of polyethylene glycolated triphenylphosphine(PEG-TPP)by a amidation reaction.Followed by loading methylene blue(MB)photosensitizer,the drug loaded nanofibers(TPP-PEG-CS@IONPs NFs)are obtained,which can be excited with 638 nm laser to generate heat and singlet oxygen,thus destroying cancerous cells in-vitro and in-vivo via its photosensitizing property.The model anticancer drugs doxorubicin(DOX · HC1)and genistein(Ge)encapsulated onto the surface of these NFs with a high drug loading capacity(35%,wt/wt),could be rapidly released at low pH.Furthermore,MB-loaded NFs could be internalized in the tumor cells efficiently,and thus release MB inside the cells to improve photo-dynamic cancer treatment.Meanwhile,IONPs can convert light radiation into thermal energy to cause local damage to tumor cells or tissues.The self-assembled NFs exhibite superior biocompatibility,good photo-stability,and encouraging photothermal performance with enhanced generation of ROS under laser irradiation.In addition,the use of MB-loaded nanofibers significantly inhibite tumor growth after tail vein injection.Based on the above results,the MB-loaded NFs show notable targeting and PDT/PTT dual therapeutic effects for tumor diagnosis and treatment with low cytotoxicity and negligible in vivo toxicity.(3)It is of great scientific significance and magnificent potential for application to explore the method of decomposition-self-assembly in-situ detection material enrichment with benefits of high sensitivity,low cost and multi-scale stimulus response based on conventional detection principle.Here,exquisite and ultra-long(>2 μm)hybrid polymer nanorods(NRs)are prepared by simple self-assembly of a phenylboronic acid modified genistein crosslinker(Ge-di(HMPBA-pin))and D-a-tocopheryl polyethylene glycol 1000(TPGS).The obtained NRs exhibit quantitative and sensitive colorimetric detection of H2O2 with significant different detection limits for different stromal materials.More significantly,the presence of H2O2 triggers a distinct morphological transformation of the polymer NRs assembly into the secondary structure of micelles via the oxidative deboronation of boronate moieties in HMPBA-pin-SA.At the same time,it spontaneously induces the aggregations of metal nanoparticles(Au NPs),metal nanorods(Au NRs),quantum dots(MoS2 QDs),metal ions(Cu2+),protein(ferritin)and tetraphenylethene(TPE)molecules,giving rise to a dramatic stimuli-triggered open/close switchable complexation and apparent colorimetric transitions in vitro.This study,for the first time,showcases the fascinating advantages of such unprecedented secondary structure-induced aggregation and uncovers the immense potential to design a plethora of other sensing systems by virtue of the alternate trigger-specific,sacrifice-aggregated building moieties.