Photodynamic therapy(PDT)is a clinically representative treatment strategy for cancer.However,conventional photosensitizers(PSs)are usually hampered by poor water solubility and low targeting capacity.Here,we report t...Photodynamic therapy(PDT)is a clinically representative treatment strategy for cancer.However,conventional photosensitizers(PSs)are usually hampered by poor water solubility and low targeting capacity.Here,we report the precise molecular engineering of aptamer oligonucleotides to solubilize hydrophobic near-infrared(NIR)PSs for enhanced cancer PDT.Hydrophobic pyropheophorbide A(PA)is precisely conjugated to aptamer oligonucleotides by combing DNA solid-phase synthesis technology and Cu-free click chemistry.Precise coupling of insoluble PA to hydrophilic aptamer oligonucleotides vastly improves its solubility to as high as 750μM in water without any cosolvent,resulting in an enhanced NIR fluorescence property(quantum yield=23%)and photoactivity.Moreover,the targeting ability of aptamer oligonucleotides is not affected by our molecular engineering strategy.Abundant reactive oxygen species(ROS)are produced intracellularly with 660 nm laser irradiation,eliciting mitochondria damage and cell death.Tumor growth is effectively inhibited with a single dose of aptamer-PA conjugates without in vivo toxicity.Their therapeutic effect is more than 20-fold higher than that of PA.Compared with traditional formulation,using aptamer oligonucleotides as functional carriers to solubilize hydrophobic NIR PSs is more precise and operable.Our DNA molecular engineering strategy paves a way for the rational design of molecularly targeted medicine for future clinical cancer therapy.展开更多
基金supported by National Key R&D Program of China(grant no.2020YFA0210800)National Natural Science Foundation of China(grant nos.52161160307 and 22205139)+3 种基金Natural Science Foundation of Shanghai(grant no.22ZR1437800)Shanghai Sailing Program(grant no.20YF1424500)Innovative Research Team of High-Level Local Universities in Shanghai,Excellent Academic Leader Programme of Shanghai Health Commission(grant no.2022XD033)Core Facility of Basic Medical Sciences in Shanghai Jiao Tong University School of Medicine.
文摘Photodynamic therapy(PDT)is a clinically representative treatment strategy for cancer.However,conventional photosensitizers(PSs)are usually hampered by poor water solubility and low targeting capacity.Here,we report the precise molecular engineering of aptamer oligonucleotides to solubilize hydrophobic near-infrared(NIR)PSs for enhanced cancer PDT.Hydrophobic pyropheophorbide A(PA)is precisely conjugated to aptamer oligonucleotides by combing DNA solid-phase synthesis technology and Cu-free click chemistry.Precise coupling of insoluble PA to hydrophilic aptamer oligonucleotides vastly improves its solubility to as high as 750μM in water without any cosolvent,resulting in an enhanced NIR fluorescence property(quantum yield=23%)and photoactivity.Moreover,the targeting ability of aptamer oligonucleotides is not affected by our molecular engineering strategy.Abundant reactive oxygen species(ROS)are produced intracellularly with 660 nm laser irradiation,eliciting mitochondria damage and cell death.Tumor growth is effectively inhibited with a single dose of aptamer-PA conjugates without in vivo toxicity.Their therapeutic effect is more than 20-fold higher than that of PA.Compared with traditional formulation,using aptamer oligonucleotides as functional carriers to solubilize hydrophobic NIR PSs is more precise and operable.Our DNA molecular engineering strategy paves a way for the rational design of molecularly targeted medicine for future clinical cancer therapy.
