Recent progress of aptamer-drug conjugates in cancer therapy

Aptamers are single-stranded DNA or RNA sequences that can specifically bind with the target protein or molecule via specific secondary structures.Compared to antibody-drug conjugates(ADC),aptamer-drug conjugate(ApDC)is also an efficient,targeted drug for cancer therapy with a smaller size,higher chemical stability,lower immunogenicity,faster tissue penetration,and facile engineering.Despite all these advantages,several key factors have delayed the clinical translation of ApDC,such as in vivo off-target effects and potential safety issues.In this review,we highlight the most recent progress in the development of ApDC and discuss solutions to the problems noted above.

Molecular Engineering of Aptamer to Solubilize Hydrophobic Near-Infrared Photosensitizer for Enhanced Cancer Photodynamic Therapy

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.