A supramolecular nano-delivery system based on AIE PARP inhibitor prodrug and glycosylated pillar[5]arene for drug-resistance therapy.
Manman YangKe YangBingling GaoPeng WangTianjiao LiYi ZhengYuxin PeiZhichao PeiYinghua LvPublished in: Chemical communications (Cambridge, England) (2022)
A supramolecular nano-delivery system GP5⊃Pro-ANI based on the host-guest complex of glycosylated pillar[5]arene (GP5) and an amide linked fluorescent PARP inhibitor (4-amino-1,8-naphthimide, ANI) was constructed. The PARP inhibitor ANI, capable of inhibiting the ability of DNA damage repair, was modified into an AIE prodrug (Pro-ANI), which allows for the visualization of real-time cancer cellular drug uptake tracing and selective drug release. In vitro studies revealed that the DOX-loaded GP5⊃Pro-ANI achieved targeted drug delivery and dual-drug synergistic chemotherapy for DNA repair interference and tumor DNA collapse aggravation, which enhanced the chemosensitivity and overcame tumor drug resistance and migration. This strategy paves a new avenue for utilizing PARP inhibitors to construct AIE supramolecular nano-delivery systems for drug uptake visualization and synergistic chemotherapy.
Keyphrases
- dna repair
- dna damage
- cancer therapy
- drug delivery
- drug release
- water soluble
- living cells
- dna damage response
- fluorescent probe
- anti inflammatory
- oxidative stress
- adverse drug
- locally advanced
- signaling pathway
- energy transfer
- drug induced
- papillary thyroid
- stem cells
- single molecule
- circulating tumor
- wastewater treatment
- radiation therapy
- squamous cell carcinoma
- mesenchymal stem cells
- single cell
- bone marrow
- circulating tumor cells