Abstract
Polyamine detection and depletion have been extensively investigated for cancer prevention and treatment. However, the therapeutic efficacy is far from satisfactory, mainly due to a polyamine compensation mechanism from the systemic circulation in the tumor environment. Herein, we explore a new solution for improving polyamine detection as well as a possible consumption therapy based on a new photosensitizer that can efficiently consume polyamines via an irreversible chemical reaction. The new photosensitizer is pyrrolopyrroleaza-BODIPY pyridinium salt (PPAB-PyS) nanoparticles that can react with the over-expressed polyamine in cancer cells and produce two photosensitizers with enhanced phototoxicity on cancer destruction. Meanwhile, PPAB-PyS nanoparticles provide a simultaneous ratiometric fluorescence imaging of intracellular polyamine. This combination polyamine consumption with a chemical reaction provides a new modality to enable polyamine detection along with photodynamic therapy as well as a putative depletion of polyamines for cancer treatment and prevention.
Highlights
Polyamine detection and depletion have been extensively investigated for cancer prevention and treatment
In the polyamine biosynthesis pathway, putrescine is formed by the action of ornithine decarboxylase (ODC) and is converted into subsequent polyamines by the addition of aminopropyl groups in reactions catalyzed by spermidine synthase and spermine synthase[3]
The concept is based on pyrrolopyrrole aza-BODIPY pyridinium salt (PPAB-PyS) nanoparticles that can react with the overexpressed polyamine in cancer cells and produce two photosensitizers (DPP-PyS and compound 3) with strong reactive oxygen species (ROS) generation capability for more effective cancer cell destruction
Summary
Polyamine detection and depletion have been extensively investigated for cancer prevention and treatment. PPAB-PyS nanoparticles provide a simultaneous ratiometric fluorescence imaging of intracellular polyamine This combination polyamine consumption with a chemical reaction provides a new modality to enable polyamine detection along with photodynamic therapy as well as a putative depletion of polyamines for cancer treatment and prevention. The caught polyamines may be released back to the cells as the host–guest interaction is reversible To overcome these disadvantages, developing a novel, irreversible polyamine depletion strategy for cancer therapy is urgently required. The chemical reaction of this photosensitizer with polyamines generates two photosensitizers that can produce more reactive oxygen species (ROS) for synergistic cancer destruction
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