ABSTRACT
To obtain near-IR absorbing biomaterials as fluorescence cellular imaging and anticancer agents for hypoxic cancer cell, a nano NIR fluorescence Mn(III/IV) polymer (PMnD) was spectroscopically characterized. The PMnD shows strong emission at 661nm when excited with 643nm. Furthermore, PMnD can catalyze water oxidation to generate dioxygen when irradiated by red LED light (10W). In particular, the PMnD can enter into HepG-2 cells and mitochondria. Both anticancer activity and the inhibition of the expression of HIF-1α for PMnD were concentration dependent. Our results demonstrate that PMnD can be developed as mitochondria targeted imaging agents and new inhibitors for HIF-1 in hypoxic cancer cells.
Subject(s)
Antineoplastic Agents/pharmacology , Boron Compounds/pharmacology , Manganese/pharmacology , Polymers/pharmacology , Spectroscopy, Near-Infrared , Water/chemistry , Catalysis , Cell Death/drug effects , Cell Proliferation/drug effects , Hep G2 Cells , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Manganese/physiology , Molecular Imaging , Oxidation-Reduction , Oxygen/metabolism , Spectrometry, Fluorescence , Spectrophotometry, UltravioletABSTRACT
Hypoxia promotes not only the metastasis of tumors but also therapeutic resistance. Photosensitizer-mediated consumption of O2 during photodynamic therapy (PDT) reinforces tumor hypoxia. Herein, a light-dependent attenuator of a hypoxic environment is reported for accurate MRI and phototherapy of hypoxic cancer. First, a photoresponsive Mn(ii) nanoassembly was constructed, then it was assembled with bovine serum albumin (BSA) and modified with polyethylene glycol-folic acid (PEG-FA), forming cancer targeting Mn-DBA@BSA-FA nanoassemblies, which offer T1 signals and can catalyze the water oxidation reaction under irradiation of red light emitting diode (LED) light with the generation of O2 and heat. Moreover, they could selectively penetrate through and accumulate in the tumor tissues with clear T1 magnetic resonance imaging (MRI) signals, and have remarkably eliminated the tumors in vivo, while they are of low toxicity to the healthy organs. The release of the Mn(ii) complex from the nanoparticles in an acidic environment and the in vivo biodistribution results confirm the selective cancer targeting. Our work demonstrates the potential of nanoparticles as excellent theranostic agents for MR imaging combined with phototherapy triggered by near-infrared light.
ABSTRACT
A new type of fluorescent silver nanoclusters consisting of one silver bound to several strands of DNA, called multi-DNA-AgNCs, have been constructed using a bifunctional oligonucleotide with the recognition sequence 5'-CTAC[combining low line]G[combining low line]T[combining low line]G[combining low line]CT-3' as a stabilizing agent. The target oligonucleotide causes the multi-DNA-AgNCs to reassemble into smaller sized Ag clusters with quenched emission properties, while BSA induces the reassembly of the multi-DNA-AgNCs to give large particles with an enhanced emission. This demonstrates that the multi-DNA-AgNCs can specifically detect this recognition sequence. Furthermore, the multi-DNA-AgNCs show different fluorescence responses toward the total protein of normal cells (WRL-68), HepG-2 cells and HepG-2 cells incubated with 5-fluorourcil (5-Fu). The results show that the total protein of the HepG-2 cells, in which HIF is highly expressed, significantly decreases the fluorescence emission. Consequently, the multi-DNA-AgNCs can be used as a fluorescence probe for the detection of cancer cells, which have a high expression of HIF.