RESUMO
Photodynamic therapy (PDT) is a promising cancer therapy modality due to its intrinsically negligible side effects and treatment resistance. However, the development of the high-efficiency PDT still remains a challenge. Herein, a nanodrug platform PEG-Ce6-PEI@PB combined tumor acidity-induced polyethyleneimine (PEI) cytotoxicity with an oxygen self-supply property is developed for dual-enhanced PDT. The obtained PEG-Ce6-PEI@PB presents suppressed PEI cytotoxicity and chlorin e6 (Ce6) phototoxicity during the bloodstream before becoming active in tumor tissues/cells. The acidic tumor microenvironment can shed PEG coating to rebound PEI positive charges, facilitating tumor cell uptake and reverting the PEI cytotoxicity to enhance following PDT. Moreover, Prussian blue (PB) nanozymes with catalase-like activity can convert endogenous hydrogen peroxide into oxygen to relieve tumor hypoxia, which is attributed to the photosensitizer Ce6 producing more cytotoxic reactive oxygen species upon laser irradiation to further strengthen PDT. Moreover, PEG-Ce6-PEI@PB exhibits good biocompatibility and long blood circulation. More importantly, PEG-Ce6-PEI@PB-treated breast cancer cells and tumor-bearing mice present effective therapeutic efficacy upon laser irradiation, verifying the synergistic antitumor effects of PEI cytotoxicity and oxygen self-supplying PDT.
Assuntos
Nanopartículas , Fotoquimioterapia , Animais , Ferrocianetos , Camundongos , Oxigênio , Polietilenoglicóis , Polietilenoimina , Hipóxia TumoralRESUMO
ROS is a significant factor in the cancer treatment mechanism. The monitoring anticancer-associated H2O2 level plays a vital role in the anticancer mechanistic exploration in pathology and physiology. Herein we synthesized a ratiometric fluorescent probe (HBQ-L) to detect and image H2O2 based on excited-state intramolecular proton transfer. HBQ-L had a high sensitivity (231-fold) with a low detection limit (28.5 nM) for monitoring H2O2 in solution. HBQ-L showed good mitochondrial-targeting and successfully detected both exo-/endogenous H2O2 in A549 cells. Furthermore, HBQ-L was used to ratiometric monitor H2O2 level in anticancer reagent DOX-treated cells or zebrafish. Importantly, it was employed to access the monitoring H2O2 in the A549 tumor-bearing mice.
Assuntos
Corantes Fluorescentes , Peróxido de Hidrogênio , Animais , Camundongos , Prótons , Espectrometria de Fluorescência , Peixe-ZebraRESUMO
In the classical amidation between aromatic ketones and amines, 2.0 equivalents of amines are necessarily required to gain satisfying yields. The specific role of the amine in the direct amidation already puzzled us for a long time. In this work, we disclosed that the amine acts as both reactant and catalyst. Specifically, the determination of reaction intermediates revealed the full mechanism, based on which, the introduction of one equivalent base in the amidation is showcased here that a high yield (â¼95 %) can be afforded using only 1.1â equiv. of amine.