Subcellular-Targeted Near-Infrared-Responsive Nanomedicine with Synergistic Chemo-photothermal Therapy against Multidrug Resistant Cancer.
Zhaomin TangWeijun TianHongyu LongShuting JiangJianqing ZhaoJianren ZhouQian HeXia LuoPublished in: Molecular pharmaceutics (2022)
Multidrug resistance (MDR) is a major obstacle to effective cancer treatment. Therefore, developing effective approaches for overcoming the limitation of MDR in cancer therapy is very essential. Chemotherapy combined with photothermal therapy (PTT) is a potential therapeutic option against MDR. Herein, we developed a subcellular-targeted near-infrared (NIR)-responsive nanomedicine (Fe 3 O 4 @PDA-TPP/S 2 -PEG-hyd-DOX, abbreviated as Fe 3 O 4 -ATSPD) as a new photothermal agent with improved photothermal stability and efficiency. This system demonstrates high stability in blood circulation and can be accumulated at the tumor site by magnetic targeting enhanced permeability and retention effect (EPR). Near-infrared (NIR) irradiation at the tumor site generates a photothermal effect from the photosensitizer Fe 3 O 4 @PDA, leading to a dramatic decrease in mitochondrial membrane potential. Simultaneously, the conjugated drugs released under low pH condition in endosomes or lysosomes cause nucleus DNA damage and cell apoptosis. This subcellular-targeted NIR-responsive nanomedicine with efficient integration of diagnosis and therapy could significantly enhance MDR cancer treatment by combination of chemotherapy and PTT.
Keyphrases
- cancer therapy
- multidrug resistant
- photodynamic therapy
- drug delivery
- drug release
- drug resistant
- gram negative
- dna damage
- acinetobacter baumannii
- fluorescence imaging
- klebsiella pneumoniae
- oxidative stress
- fluorescent probe
- cell proliferation
- radiation therapy
- squamous cell
- dna repair
- mass spectrometry
- bone marrow
- drug induced
- climate change
- mesenchymal stem cells