| As a near-infrared fluorescent dye,indocyanine green(ICG)has been used in the early detection of some diseases,and its photosensitive characteristics cause the photothermal and photodynamic effects triggered by near-infrared laser(NIR),which can destroy the tumor.However,the application of ICG in biomedicine is limited because of its poor stability,including aggregation,photodegradation,thermal degradation and nonspecific binding with proteins in blood circulation,lack of targeting specificity and rapid clearance of tumor lesions in vivo.Paclitaxel(PTX)is a microtubule stabilizer widely used in the treatment of ovarian cancer,breast cancer and cervical cancer,but its problems such as drug resistance,water solubility and targeting have seriously affected its clinical application.Therefore,new multifunctional nanoparticles that organically integrate a variety of therapeutic methods have become one of the research hotspots.As a natural biomaterial,albumin is biocompatible,non-immunogenic and biodegradable which can enter the tumor stroma via gp60 mediated endocytosis,followed by combining with secreted protein acidic and rich in cysteine(SPARC),so it can be used as an excellent carrier for loading antitumor drugs.In this work,using human serum albumin coupled with multiple E-selectin peptide ligands(CIELLQAR)and polyethylene glycol(PEG)as the carrier,PTX and ICG were loaded through hydrophobic interaction,and a nano platform PTX/ICG@HSA-PEP-PEG NPs with targeted effects of combined chemotherapy,photothermal therapy and photodynamic therapy was constructed.The best dosage mass ratio was selected as HSA:ICG: PTX = 20:1:4.The encapsulation efficiency(EE%)and drug loading(DL%)of ICG in nanoparticles were 98.49 ± 0.66% and 3.96 ± 0.22%,respectively;The EE% and DL%of PTX were 98.19 ± 3.13% and 6.59 ± 0.08%,respectively.TEM images showed that the target nanoparticles were spherical with uniform morphology.The results of dynamic light scattering(DLS)showed that the particles had an average size of 104±1.48 nm and a negative surface charge of-28.7±1.32 m V.The stability of nanoparticles is good,the freezedried powder can be stored stably for a long time,and there is no obvious change in the properties within 7 days after redissolution.In vitro drug release experiment showed that the rate of PTX release from nanoparticles irradiated by near-infrared laser was significantly higher than that without laser irradiation.In vitro photothermal performance evaluation experiment found that the temperature rise range of PTX/ICG@HSA-PEP-PEG NPs(ICG: 25 μg/m L)was more than 30 ℃ after laser irradiation for 5 minutes,and it showed ICG concentration dependence in a certain range.In vitro photodynamic effect experiments showed that nanoparticles can produce reactive oxygen species(ROS)under laser irradiation,and the photodynamic conversion efficiency of nanoparticles is higher than that of free ICG.MTT assay showed that the nanoparticles had high toxicity on HUVEC(stimulated by TNF-α)with high expression of E-selectin.In vivo fluorescence imaging experiments showed that nanoparticles prolong the circulation time and show a certain tumor targeting.To sum up,this paper studies a kind of nanoparticles with multiple functions such as chemotherapy,photothermal therapy and photodynamic therapy,and has a variety of tumor targeting effects.This particle is expected to play an efficient synergistic therapeutic effect on tumors. |
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