A nanoplatform based on allylthiopurine bio-MOF and glycosylated AIE PARP inhibitor for cancer synthetic lethal therapy.
Bingling GaoKe YangManman YangWendong LiTingli JiangRong GaoYuxin PeiZhichao PeiYinghua LvPublished in: Chemical communications (Cambridge, England) (2024)
A biological nanoplatform (Gal-ANI@ZnAP NPs) was constructed based on a prodrug-skeletal metal-organic framework (MOF) using purine nucleobase analogue prodrug 6-allylthiopurine as a bioactive ligand, and functionalized with AIE fluorescent PARP inhibitor glycoconjugate for visualization therapy and synthetic lethal cancer therapy. This nanoplatform could actively target cancer cells, selectively release drugs in response to esterase/pH, and visualize drug uptake. In vitro studies revealed that Gal-ANI@ZnAP NPs increased the synthetic lethality in cancer cells by inducing DNA repair failure with the simultaneous targeting of PARP and nucleotide metabolism, thereby exhibiting a significant cancer-killing effect. The study presents a novel strategy to construct an AIE nanoplatform using pharmaceutical molecules for drug uptake visualization and boosting synthetic lethality in cancer.
Keyphrases
- cancer therapy
- dna repair
- drug delivery
- metal organic framework
- dna damage
- papillary thyroid
- drug release
- photodynamic therapy
- living cells
- squamous cell
- stem cells
- childhood cancer
- quantum dots
- emergency department
- mass spectrometry
- oxidative stress
- drug induced
- high resolution
- young adults
- wastewater treatment
- single cell
- case control