Phototherapy as one effective antitumor therapeutic modality has attracted increasing attention due to its advantages including low side effects,negligible drug resistance,and non-invasive nature.The key element of phototherapy is phototherapeutic agent.Therefore,how to construct phototherapeutic agent to meet the desired demands of imaging and treatment has become a research hotspot in phototherapy.Among the numerous explored fluorescent probes and phototherapy nanodrugs,organic fluorescent dyes are particularly promising because of their intrinsic biodegradability and good biocompatibility.However,organic fluorescent dye has some problems such as low bioavailability in physiological environment,easy photobleaching,and non-targeting,while the long-term toxicity and poor stability of most drug carriers restrict its performance in imaging and therapy.Based on this,we constructed a series of functional nanomaterials with safety and stability in physiological environment through covalent bond and non-covalent bond collaborative self-assembly from simple biological small molecules to solve the problems in the application of organic dyes in imaging and phototherapy.The specific research contents are mainly divided into the following four aspects:(1)Small biomolecule tannic acid(TA)and Fe(III)spontaneously formed adhesion layer at the Chlorin e6(Ce6)nanocolloids interface through coordination polymerization to prepare Ce6@TA-Fe(III)nanoparticles with good dispersion.The prepared Ce6@TA-Fe(III)NPs has good colloidal stability,biocompatibility,biodegradability and high drug loading.The strongly aggregated state of Ce6 in Ce6@TA-Fe(III)NPs results in fluorescence quenching and a reduced ROS generation ability in vivo under blood circulation.However,fluorescence and ROS generation ability of Ce6 are recovered after cellular internalization,and achieve high efficiency photodynamic therapy guided by imaging in vivo.(2)Amphiphilic amino acids(DSP)were synthesized and self-assembled into stable and biodegradable nanoparticles by covalently cross-linking with genipin.The nanoparticles exhibit self-fluorescence characteristics in the red light region.After loading photothermal agent indocyanine green,the nanoparticles are used for fluorescent imaging guided photothermal therapy.Amphiphilic amino acid as building unit is composed of phenylalanine and disulfide bond groups.The strong hydrophobicity of phenylalanine ensures that the reaction can trigger assembly to form stable nanoparticles,while the disulfide bond can be broke by the over-expressed glutathione in tumor cells,ensures the controllable degradation of nanoparticles.Importantly,the covalent reaction product-genipin blue(assembly unit)has auto-fluorescence properties,so the particle can be used as a probe for fluorescence imaging as well as a drug carrier.The ICG-loaded nanoparticles possessed high photothermal conversion efficiency,and showed an enhanced photothermal effect in the near-infrared region.(3)Photothermal nanoparticles with broad spectrum absorption(UV to near infrared region)were prepared by the combination of covalent and non-covalent interactions of hydrophobic cationic phenylalanine dipeptide and small molecule genipin as building blocks.A series of nanoparticles of different sizes were prepared by regulating the thermodynamic process(reaction temperature)between dipeptide and small molecule genipin.The fluorescence of nanoparticles is effectively quenched and has high photothermal conversion efficiency and excellent photostability.For the first time,the photothermal nanodrugs with high photothermal conversion efficiency were prepared by covalent assembly of nonpigmented biological small molecules for photothermal therapy guided by photoacoustic imaging.(4)Nonpigmented hydrophobic cationic dipeptide and small molecule glutaraldehyde(GA)undergo Schiff base reaction,and the reaction product is used as the initial building units and self-assemble into nanoparticles driven by non-covalent interaction(hydrophobic,hydrogen bond).A series of nanoparticles with adjustable fluorescence emission(blue-green-red)were prepared by regulating the reaction kinetically process(the reaction time)between peptide and glutaraldehyde.The results showed that the fluorescence signal of the nanoparticles was generated by the Schiff base bond(C=N)and the double bond(C=C)formed during the reaction.More importantly,by increasing the reaction time,the Schiff base bond of the assembled units was dominant,and the emission spectrum shifted into the longer wavelength.Moreover,these interesting NPs exhibited outstanding stability under physiological conditions,good degradability and low toxicity,achieved sustainable fluorescence imaging in cancer cells. |