| Cancer is one of the most important health problems worldwide and is the second leading cause of death worldwide.In clinical practice,photodynamic therapy（PDT）is one of the most important methods and a promising treatment method.Compared with conventional clinical treatments,PDT has the advantages of less side effects,less invasiveness,shorter duration,the ability to destroy tumor-associated vasculature,the ability to be precisely targeted,repeated many times,little scarring after healing,and low cost.The development of photodynamic therapy is described in detail in this paper.At present,hematoporphyrin is the most commonly used photosensitizer in clinical practice.Its biocompatibility is good,but its specificity is poor,easy to disperse in human tissues for a long time,produce phototoxicity,patients need to avoid light for a long time during the treatment process,and the preparation process is complex and expensive.Therefore,how to improve the specific targeting ability of hematoporphyrin and reduce the cost is particularly important.Therefore,in this study,we proposed to modify hematoporphyrin by tumor microenvironment responsive polyamino acids with good biocompatibility,in order to improve its specific targeting and enrichment ability for tumors and reduce production costs.Based on this,this paper first prepared nanoparticles（PCys-Hemin）with different particle sizes by reverse-phase emulsion method with polycysteine and hemin,and then removed ferric iron ions by formate-iron powder method.The tumor microenvironment responsive poly（（L-glutamic acid-L-tyrosine）-L-threonine-L-cysteine）（PGTTCs-6.6）was modified by ring-opening polymerization of N-carbonyl endocyclic anhydride（NCA）initiated by hexamethyldisilanyl amine lithium.PCys-Hp-PGTTCs-6.6 nanomaterial with gelation ability of tumor microenvironment and photodynamic therapy ability was obtained.The results of the morphology and iron removal efficiency of the microspheres showed that the prepared microspheres were spherical,and the removal rate of Fe3+was up to 91%.The PGTTCs-6.6 modified microspheres were p H responsive.Under the irradiation of 630 nm wavelength light source,the nanospheres showed strong singlet oxygen release ability and phototoxicity.The experimental results showed that PCys-Hp-PGTTCs-6.6 could be enriched in the tumor site,indicating that PCys-Hp-PGTTCs-6.6 had a good targeting aggregation ability.After 30±5 days of treatment,the tumor gradually atrophied and disappeared,indicating that PCys-Hp-PGTTCs-6.6 had embolization treatment ability.After irradiation with a630 nm wavelength light source for 3 hours,the tumor could completely shrink and disappear within 20±5 days,indicating that the 630 nm wavelength light source has a photodynamic therapy effect and can improve the efficiency of tumor treatment.Due to the large size of the microspheres,their permeability to the tumor is limited.In order to improve the permeability of the photosensitizer,The paper also uses ultrasonic assisted hydrochloric acid-acetic anhydride-iron sulfate salt system to remove the ferric iron of hemin chloride to get protoporphyrin and poly[（L-glutamic acid-cysteine）-L-threonine]-sulfhydryl-6.5（PTGCs-6.5）through the double bond and sulfhydryl"click reaction",The p H responsive polyamino acid modified hematoporphyrin Hp-PTGC-SS-TGA-6.5 was prepared.The product was characterized by a series of tests,including its structure,singlet oxygen release ability,phototoxicity and cytotoxicity,and its therapeutic effect was tested in H22 tumor-bearing mice.The results of in vivo fluorescence imaging showed that Hp-PTGC-SS-TGA-6.5 could be enriched in the tumor site and had targeting ability.The tumor gradually atrophie and disappear about 25±5days after treatment,indicating that HP-PTGC-SS-TGA-6.5 had embolization treatment ability.After irradiation with a 630 nm wavelength light source for 3 hours,the tumor could completely shrink and disappear within 20 days.In summary,the composite material can realize the integration of catheter-free embolization and photodynamic therapy. |
