| Photodynamic therapy?PDT?,as a new type of non-invasive tumor treatment,has unique therapeutic characteristics such as small toxic side effects,good reproducibility,non-drug resistance,low cost,and safety and effectiveness.It has widely used in the clinical treatment of various cancers.Specific wavelengths of light,tissue oxygen,and photosensitizer?PS?are the three elements of PDT.Among them,the key element is PS,which playes a vital role in photodynamic therapy.Porphyrin derivatives have strong absorption in PDT treatment window?650?850 nm?,which are widely used as photosensitizers in the diagnosis and treatment of cancer.However,most of them are aromatic molecules with strong hydrophobicity and poor water-solubility,low specificity and most of them are easy to aggregate in vivo,causeing the PDT effect to weaken;Theother,hypoxia is a major feature of tumor microenvironment.Further aggravating tumor hypoxia and inhibiting further treatment of PDT.To solve these problems,the structure of porphyrin derivatives was modified to enhance their specificity.By building a nano-drug delivery system to improve its water solubility and dispersibility,to improve biocompatibility and achieve precise targeting.We used the tetracarboxytetraphenylporphyrin?TCPP?as a raw material,modified with mitochondrial targeting molecule triphenylphosphonium?TPP?into its structure,and then loaded into the folic acid-modified graphene oxide nano-drug delivery system formed GO-FA@TCPP-TPP nanoparticles?GF@TCPP-TPP NPs?.And the physical and chemical characterization and evaluation of the antitumor activity of PDT were performed.In vitro photodynamic biological experiments showed that the GF@TCPP-TPP NPs with well water solubility and biocompatibility enhanced the phagocytosis and photodynamic activity of HeLa cells to photosensitizers(IC50=11.91±1.10?g/mL;650±10 nm,5 mW/cm2,10min).And the GF@TCPP-TPP NPs with high dual targeting?tumor targeting,mitochondrial targeting?have been verified by biological experiments.Therefore the new targeted nano-drug delivery system?GF@TCPP-TPP?prepared in this paper provides an effective PDT treatment strategy for tumor treatment.In addition,to solve the problem that PDT treatment is limited by tumor hypoxia microenvironment,a dual-mode treatment mode of PDT-chemotherapy was constructed by utilizing the hypoxia microenvironment induced by PDT to activate the 6-aminoflavonoid,a chemotherapeutic drug that is sensitive to hypoxia to achieve dual-mode tumor treatment.A nano-platform(d-TiO2-X@SiO2\PPa\AF@PEG NPs)was constructed by combining visible light-responsive PDT and hypoxia-activated chemotherapy to enhance the anti-cancer effect.Defective inorganic semiconductor d-TiO2-X nanomaterials and organic photosensitizer PPa are excited at 650 nm visible light,play a PDT role together,intensify the consumption of oxygen,create a severe hypoxia environment in the cell,activate the cancer inhibitor AF to play an anti-cancer role effect.Developed PDT-chemotherapy nanocomposite(d-Ti O2-X@SiO2\PPa\AF@PEG NPs)has low dark toxicity,excellent biological activity and well fluorescence imaging ability,and can effectively generate reactive oxygen species?ROS?in cells.The results of AM-PI cell staining experiments showed that PDT-induced hypoxia-activated chemotherapy synergistically enhanced anticancer ability.Such a strategy based on PDT leading to tumor hypoxia-activating drugs to enhance their anti-cancer capacity is an effective way to solve the hypoxia-inhibiting PDT treatment and general chemotherapy toxicity.Further research shows that d-Ti O2-X@SiO2\PPa\AF@PEG NPs was expected to become a new high-efficiency multi-modal treatment nano platform. |
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