The objective of this study was to evaluate the targeted T1-magnetic resonance imaging (MRI), quantitative biodistribution and toxicity of aptamer (AS411) conjugated Mn3O4@SiO2 core-shell nanoprobes (NPs) in human cervical carcinoma tumor-bearing mice. The NPs were firstly prepared by encapsulating a hydrophobic Mn3O4 core within an amino functionalized silica shell. The fluorophore rhodamine (RB) was doped into the silica shell and the amphiphilic polymer poly(ethylene glycol) (PEG) was modified on the surface of the shell to improve its biocompatibility, then the aptamer AS411 was conjugated onto the end of the PEG chains as targeting ligands. The final NPs were abbreviated as Mn3O4@SiO2(RB)-PEG-Apt. By means of in vitro fluorescence confocal imaging and in vivo MRI, the NPs have been demonstrated to target cancer cells and prominent tumor aggregation effectively. The imaging results were further confirmed by a quantitative biodistribution study. In addition, histological, hematological and biochemistry analysis also proved the low toxicity of NPs in vivo. Our results showed the great potential of the Mn3O4@SiO2(RB)-PEG-Apt NPs could be used as a multifunctional nanoplatform for long-term targeted imaging and therapy of cancer.

Repair of damaged DNA induced by radiation plays an important role in the development of radioresistance, which greatly restricts patients' benefit from radiotherapy. However, the relation between radioresistance development and DNA double-strand break repair pathways (mainly non-homologous end joining and homologous recombination) and how these pathways contribute to radioresistance are unclear. Here, we established a radioresistant breast cancer cell line by repeated ionizing radiation and studied the alteration in DNA repair capacity. Compared with parental sham-treated cells, radioresistant breast cancer cells present elevated radioresistance, enhanced malignancy, increased expression of Ataxia-telangiectasia mutated (ATM), and increased DNA damage repair efficiency, as reflected by accelerated γ-H2AX kinetic. These defects can be reversed by ATM inhibition or ATM knockdown, indicating a potential link between ATM, DNA repair pathway and radiosensitivity. We propose that cancer cells develop elevated radioresistance through enhanced DNA damage repair efficiency mediated by increased ATM expression. Our work might provide a new evidence supporting the potential of ATM as a potential target of cancer therapy.

Excessive iron ions in cancer cells can catalyze H 2 O 2 into highly toxic •OH and then promote the generation of reactive oxygen species (ROS), inducing cancer ferroptosis. However, the e cacy of ferroptosis catalyst is still insu cient because of low Fe(II) release, which severely limited its application in clinics. Herein, we developed a novel magnetic nanocatalyst for MRI-guided chemo-and ferroptosis synergistic cancer therapies through iRGD-PEG-ss-PEG modi ed gadolinium engineering magnetic iron oxide loaded Dox (ipGdIO-Dox). The introduction of gadolinium compound disturbed the structure of ipGdIO-Dox, making magnetic nanocatalyst be more sensitive to weak acid. When the ipGdIO-Dox entered into cancer cells, abundance of Fe(II) ions were released and then catalyzed H 2 O 2 into highly toxic OH•, which would elevate cellular oxidative-stress to damage mitochondria and cell membranes and induced cancer ferroptosis. In addition, the iRGD-PEG-ss-PEG chain coated onto nanoplatform were also broken by high expression of GSH, and then the Dox was released. This process not only effectively inhibited DNA replication, but further activated cellular ROS, making nanoplatform achieve stronger anticancer ability. Besides, the systemic delivery ipGdIO-Dox signi cantly enhanced T 1 -and T 2 -weighted MRI signal of tumor, endowing accurate diagnostic capability for tumor recognition. Therefore, the ipGdIO-Dox might be a promising candidate for developing MRI guided chemo-and chemdynamic synergistic theranostic system.

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