RESUMO
Magnetic resonance imaging (MRI) is an important tool in the diagnosis of many cancers. However, clinical gadolinium (Gd)-based MRI contrast agents have limitations, such as large doses and potential side effects. To address these issues, we developed a hydrogen-bonded organic framework-based MRI contrast agent (PFC-73-Mn). Due to the hydrogen-bonded interaction of water molecules and the restricted rotation of manganese ions, PFC-73-Mn exhibits high longitudinal relaxation r1 (5.03 mM-1 s-1) under a 3.0 T clinical MRI scanner. A smaller intravenous dose (8 µmol of Mn/kg) of PFC-73-Mn can provide strong contrast and accurate diagnosis in multiple kinds of cancers, including breast tumor and ultrasmall orthotopic glioma. PFC-73-Mn represents a prospective new approach in tumor imaging, especially in early-stage cancer.
Assuntos
Glioma , Manganês , Humanos , Meios de Contraste , Gadolínio , Imageamento por Ressonância Magnética/métodosRESUMO
Transarterial chemoembolization (TACE) is one of the most commonly used treatments for hepatocellular carcinoma (HCC); however, the poor stability of emulsified chemotherapy drugs by iodinated oil always leads to serious systemic cytotoxicity. Herein, a composite hydrogel Epi/Etpoil@MC/XG was proposed by stably distributing ethiodized poppyseed oil (Etpoil) and epirubicin (Epi) in the blend hydrogel of methylcellulose (MC) and xanthan gum (XG). Benefiting from its adjusted thermo-responsive and injectable properties, the Epi/Etpoil@MC/XG has been successfully applied in the embolization of the feeding artery for a VX2 tumor model.
Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Hidrogéis/uso terapêutico , Epirubicina/farmacologia , Epirubicina/uso terapêutico , Óleo Etiodado/uso terapêutico , ArtériasRESUMO
Rational design and construction of theranostic nanomedicines based on clinical characteristics of cervical cancer is an important strategy to achieve precise cancer therapy. Herein, we fabricate a cervical cancer-targeting gold nanorod-mesoporous silica heterostructure for codelivery of synergistic cisplatin and antiangiogenic drug Avastin (cisplatin-AuNRs@SiO2-Avastin@PEI/AE105) to achieve synergistic chemophotothermal therapy. Based on database analysis and clinical sample staining, conjugation of the AE105-targeting peptide obviously improves the intracellular uptake of the nanosystem and enhances the cancer-killing ability and selectivity between cervical cancer and normal cells. It could also be used to specifically monitor the urokinase-type plasminogen activator receptor (uPAR) expression level in clinical cervical specimens, which would be an early indicator of prognosis in cancer treatment. Under 808 nm laser irradiation, the nanosystem demonstrates smart NIR-light-triggered drug release and prominent photodynamic activity via induction of reactive oxygen species overproduction-mediated cell apoptosis. The nanosystem also simultaneously suppresses HeLa tumor growth and angiogenesis in vivo, with no evident histological damage observed in the major organs. In short, this study not only provides a clinical data-based rational design strategy of smart nanomedicine for precise treatment and rapid clinical diagnosis of cervical cancer but also contributes to the development of the clinical translation of nanomedicines.
Assuntos
Antineoplásicos , Bevacizumab , Cisplatino , Ouro , Hipertermia Induzida , Nanopartículas Metálicas , Nanotubos/química , Proteínas de Neoplasias , Neovascularização Patológica , Fototerapia , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Neoplasias do Colo do Útero , Antineoplásicos/química , Antineoplásicos/farmacologia , Bevacizumab/química , Bevacizumab/farmacocinética , Bevacizumab/farmacologia , Cisplatino/química , Cisplatino/farmacocinética , Cisplatino/farmacologia , Feminino , Ouro/química , Ouro/farmacologia , Células HeLa , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Proteínas de Neoplasias/agonistas , Proteínas de Neoplasias/metabolismo , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Neovascularização Patológica/terapia , Receptores de Ativador de Plasminogênio Tipo Uroquinase/agonistas , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapiaRESUMO
A mutifunctional ruthenium-based conjugate Ru-BSe was designed and synthesized. The Ru complex with favorable bioimaging function was covalently linked with a cancer-targeted molecule that could be effectively internalized by the tumor to realize enhanced theranostic effects. The pH-response of the Ru conjugate in tumor acidic microenvironment causes ligand substitution and release of therapeutic complex. This activated complex remains inert to the reducing biomolecule-glutathione and terminally locates in mitochondria, in which it triggers oxidative stress, and activates intrinsic apoptosis. Real-time monitoring reveals that this Ru conjugate could selectively accumulate in tumor tissue in vivo, which significantly suppresses tumor progression and alleviate the damage to normal organs, realizing the precise cancer theranosis.
Assuntos
Antineoplásicos/administração & dosagem , Rutênio/administração & dosagem , Selênio/administração & dosagem , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Humanos , Ligantes , Mitocôndrias , Rutênio/farmacologia , Rutênio/uso terapêutico , Selênio/farmacologia , Selênio/uso terapêutico , Transdução de Sinais , Nanomedicina Teranóstica , Microambiente Tumoral/efeitos dos fármacosRESUMO
Radiotherapy is an important regime for treating malignant tumors. There is interest in the development of radiosensitizers to increase the local treatment efficacy under a relatively low and safe radiation dose. In this study, we designed Au@Se-R/A nanocomposites (Au@Se-R/A NCs) as nano-radiosensitizer to realize synergistic radiochemotherapy based on the radiotherapy sensitization property of Au nanorods (NRs) and antitumor activity of Se NPs. In vitro studies show that the combined treatment of A375 melanoma cells in culture with NCs and X-ray induces cell apoptosis through alteration in expression of p53 and DNA-damaging genes and triggers intracellular ROS overproduction, leading to greatly enhanced anticancer efficacy. Further studies using clinically used radiotherapy equipment demonstrate that the combined treatment of NCs and X-ray significantly inhibits the tumor growth in vivo and shows negligible acute toxicity to the major organs. Taken together, this study provides a strategy for clinical translation application of nanomedicne in cancer radiochemotherapy.