RESUMO
Messenger RNA (mRNA) therapy has shown tremendous potential for different diseases including cancer. While mRNA has been extensively used in cancer vaccine development as antigen or in cancer immunotherapy as immunomodulatory agent, the combination of mRNA therapy with photodynamic therapy has not been explored in cancer treatment. Herein, we report a reactive oxygen species (ROS)-responsive polymeric nanoparticle (NP) platform for first-in-field codelivery of mRNA and photosensitizer for effective cancer treatment. We developed ROS-responsive oligomer-based polymeric NPs and applied them to test a combination of p53 mRNA and indocyanine green (ICG). The ROS-triggered disassembly of the NPs could promote mRNA translation efficiency, whereby p53 expression induced apoptosis of lung tumor cells. Meanwhile, the released ICG could lead to generation of ROS under 808 nm laser irradiation to induce photodynamic therapy. The NP codelivery of p53 mRNA and ICG demonstrated an effective and safe anti-tumor effect in a lung cancer model.
Assuntos
Neoplasias Pulmonares , Nanopartículas , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/genética , Verde de Indocianina/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Polímeros/metabolismo , Linhagem Celular TumoralRESUMO
Fluorescent lateral flow immunoassay (LFA), one tool in point of care testing (POCT) systems for breast cancer, has attracted attention because it is quick, simple, and convenient. However, samples and the constituent material exhibit autofluorescence in the visible region, which is a very large obstacle in the development of fluorescent LFAs. The autofluorescence of biological samples is scarcely found in the second near-infrared (NIR-II) range and samples scatter and absorb less NIR-II light than visible light. Here, we report an NIR-II QD-LFA platform using the NIR-II fluorescent Ag2Se quantum dots (QDs) with 1020 nm emission encapsulated into polystyrene beads as fluorescent probes. The NIR-II LFA platform was established to detect breast cancer tumour markers (CEA and CA153) within 15 min with a low limit of detection (CEA: 0.768 ng mL-1, CA153: 1.192 U mL-1), high recoveries (93.7% ~ 108.8%), and relative standard deviations (RSDs) of less than 10%. This study demonstrated the potential of NIR-II Ag2Se polystyrene beads as a fluorescent probe in LFA for rapid and accurate identification of biomarkers. They are suited for use in professional situations.
Assuntos
Neoplasias , Poliestirenos , Biomarcadores Tumorais , Corantes Fluorescentes , Imunoensaio , LuzRESUMO
Hexamethyldisiloxane (HMDO) has been developed to efficiently promote the metal-free direct coupling of an amino function of one cysteine-free peptide or protein and a C-terminal thioester of the second peptide in ionic liquids. The amide-coupling reaction proceeds smoothly under mild conditions to afford the corresponding products in good to excellent yields (63-94%). Peptide couplings were also achieved using in-situ-generated thioesters by the thioesterification of oxo esters.
Assuntos
Líquidos Iônicos/química , Peptídeos/síntese química , Proteínas/síntese química , Siloxanas/química , Modelos Moleculares , Estrutura Molecular , Peptídeos/química , Proteínas/químicaRESUMO
Complete excision of the last remaining 1-2% of tumor tissue without collateral damage remains particularly challenging. Herein, we report thiophenthiadiazole (TTD)-derived fluorophores L6-PEGnk (n = 1, 2, 5) as new-generation NIR-II (1000-1700 nm) probes with exceptional nonfouling performance and significantly high fluorescence quantum yields in water. L6-PEG2k can self-assemble into vesicular micelles and exhibited minimal immunogenicity, low binding affinities, ultralong blood circulation (t1/2 = 59.5 h), and a supercontrast ratio in vivo. Most importantly, L6-PEG2k achieved excellent in vivo CT-26 and U87MG tumor targeting and accumulation (>20 d) through intraperitoneal or intravenous injection. A subcutaneous U87MG tumor and orthotopic brain glioma were successfully resected under NIR-II FIGS in our animal model via intraperitoneal injection in an extended time window (48-144 h). This study highlights the potential of using L6-PEG2K as self-assembling molecular probes with long-circulation persistence for routine preoperative tumor assessment and precise intraoperative image-guided resection.
Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Meios de Contraste/química , Corantes Fluorescentes/química , Glioma/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Animais , Neoplasias Encefálicas/terapia , Linhagem Celular Tumoral , Meios de Contraste/síntese química , Meios de Contraste/farmacocinética , Desenho de Fármacos , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/farmacocinética , Glioma/terapia , Meia-Vida , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Polietilenoglicóis/química , Teoria Quântica , Cirurgia Assistida por Computador , Distribuição Tecidual , Transplante HeterólogoRESUMO
The clinical success of cisplatin ushered in a new era of the application of metallodrugs. When it comes to practice, however, drug resistance, tumor recurrence, and drug systemic toxicity make it implausible to completely heal the patients. Herein, we successfully transform an electron acceptor [1, 2, 5]thiadiazolo[3,4-g]quinoxaline into a novel second near-infrared (NIR-II) fluorophore H7. After PEGylation and chelation, HL-PEG2k exhibits a wavelength bathochromic shift, enhanced photothermal conversion efficiency (41.77%), and an antineoplastic effect against glioma. Its potential for in vivo tumor tracking and image-guided chemo-photothermal therapy is explored. High levels of uptake and high-resolution NIR-II imaging results are thereafter obtained. The hyperthermia effect could disrupt the lysosomal membranes, which in turn aggravate the mitochondria dysfunction, arrest the cell cycle in the G2 phase, and finally lead to cancer cell apoptosis. HL-PEG2k displays a superior biocompatibility and thus can be a potential theranostic platform to combat the growth and recurrence of tumors.
Assuntos
Complexos de Coordenação/química , Raios Infravermelhos , Rutênio/química , Apoptose/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Linhagem Celular Tumoral , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Desenho de Fármacos , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Corantes Fluorescentes/uso terapêutico , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Hipertermia Induzida , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Fenazinas/química , Terapia Fototérmica/métodos , Polietilenoglicóis/química , Teoria Quântica , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
NIR-II fluorophores have shown great promise for biomedical applications with superior in vivo optical properties. To date, few small-molecule NIR-II fluorophores have been discovered with donor-acceptor-donor (D-A-D) or symmetrical structures, and upconversion-mitochondria-targeted NIR-II dyes have not been reported. Herein, we report development of D-A type thiopyrylium-based NIR-II fluorophores with frequency upconversion luminescence (FUCL) at ~580 nm upon excitation at ~850 nm. H4-PEG-PT can not only quickly and effectively image mitochondria in live or fixed osteosarcoma cells with subcellular resolution at 1 nM, but also efficiently convert optical energy into heat, achieving mitochondria-targeted photothermal cancer therapy without ROS effects. H4-PEG-PT has been further evaluated in vivo and exhibited strong tumor uptake, specific NIR-II signals with high spatial and temporal resolution, and remarkable NIR-II image-guided photothermal therapy. This report presents the first D-A type thiopyrylium NIR-II theranostics for synchronous upconversion-mitochondria-targeted cell imaging, in vivo NIR-II osteosarcoma imaging and excellent photothermal efficiency.
Assuntos
Corantes Fluorescentes/química , Raios Infravermelhos , Mitocôndrias/metabolismo , Neoplasias/diagnóstico por imagem , Imagem Óptica , Terapia Fototérmica , Animais , Morte Celular , Durapatita/química , Corantes Fluorescentes/síntese química , Luminescência , Camundongos Nus , Conformação Molecular , Polietilenoglicóis/química , Espectrometria de Fluorescência , Resultado do TratamentoRESUMO
Osteosarcoma is an aggressive tumor of mesenchymal origin that is more likely to spread to the lung than others, with a major impact on patients' prognosis. The optimal imaging method that can reliably detect or exclude pulmonary metastases from osteosarcoma is still scarce. Herein, two homologous types of fluorescent probes CH1055-PEG-PT and CH1055-PEG-Affibody, which show highly promising results for targeting imaging of osteosarcoma and its lung metastasis, respectively, are designed and synthesized. It is found that the NIR-II imaging quality of CH1055-PEG-PT is far superior to that of computed tomography for the early in vivo 143B tumor imaging, and this probe-guided surgery for accurate resection of 143B tumor is further performed. The high-resolution visualization of primary and micrometastatic lung lesions of osteosarcoma by using CH1055-PEG-Affibody is also demonstrated. Therefore, the attractive imaging properties of CH1055-PEG-PT and CH1055-PEG-Affibody, including high levels of uptakes, and high spatial and temporal resolution, open up opportunities for molecular imaging and clinical translation of osteosarcoma and its lung metastasis in the unique second near-infrared window.
Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Corantes Fluorescentes/química , Neoplasias Pulmonares/diagnóstico por imagem , Imagem Óptica/métodos , Osteossarcoma/diagnóstico por imagem , Animais , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Corantes Fluorescentes/metabolismo , Corantes Fluorescentes/farmacologia , Humanos , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Nus , Osteossarcoma/patologia , Fenilpropionatos/química , Polietilenoglicóis/química , Proteínas Recombinantes de Fusão/química , Espectroscopia de Luz Próxima ao Infravermelho , Tiadiazóis/química , Distribuição Tecidual , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
A novel bright near-infrared II (NIR-II, 1000-1700 nm) fluorescent probe with excellent water-solubility, superior photostability, and excellent in vitro and in vivo biocompatibility was facilely synthesized for in vivo biomedical imaging of xenograft breast tumor and chemically induced spontaneous breast carcinoma. To the best of our knowledge, it is the first time that the superior practical applications of this NIR-II probe in dimethylbenzanthracene (DMBA)-induced rat mammary carcinoma imaging and image-guided rat carcinoma surgery were demonstrated.