RESUMO
Recent advances in bioimaging and nanomedicine have permitted the exploitation of molecular optical imaging in image-guided surgery; however, the parameters mediating optimum performance of contrast agents are not yet precisely determined. To develop ideal contrast agents for image-guided surgery, we need to consider the following criteria: (1) excitation and emission wavelengths in the near-infrared (NIR) window, (2) optimized optical characteristics for high in vivo performance, (3) overcoming or harnessing biodistribution and clearance, and (4) reducing nonspecific uptake. The design considerations should be focused on optimizing the optical and physicochemical property criteria. Biodistribution and clearance should first be considered because they mediate the fate of a contrast agent in the body such as how long after intravenous injection a contrast agent reaches the peak signal-to-background ratio (SBR) and how long the signal lasts (retention).
Assuntos
Meios de Contraste/química , Corantes Fluorescentes/química , Imagem Molecular/métodos , Imagem Óptica/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Cirurgia Assistida por Computador/métodos , Animais , Feminino , Humanos , Período Intraoperatório , Camundongos , Microscopia de Fluorescência , Transplante de Neoplasias , Tomografia por Emissão de Pósitrons , Razão Sinal-Ruído , Distribuição TecidualRESUMO
Biodegradable scaffolds have been extensively used in the field of tissue engineering and regenerative medicine. However, noninvasive monitoring of in vivo scaffold degradation is still lacking. In order to develop a real-time trafficking technique, a series of meso-brominated near-infrared (NIR) fluorophores were synthesized and conjugated to biodegradable gelatin scaffolds. Since the pentamethine cyanine core is highly lipophilic, the side chain of each fluorophore was modified with either quaternary ammonium salts or sulfonate groups. The physicochemical properties such as lipophilicity and net charge of fluorophores played a key role in the fate of NIR-conjugated scaffolds in vivo after biodegradation. The positively charged fluorophore-conjugated scaffold fragments were found in salivary glands, lymph nodes, and most of the hepatobiliary excretion route. However, halogenated fluorophores intensively accumulated into lymph nodes and the liver. Interestingly, balanced-charged gelatin scaffolds were degraded into urine in a short period of time. These results demonstrate that the noninvasive optical imaging using NIR fluorophores can be useful for the translation of biodegradable scaffolds into the clinic.
Assuntos
Implantes Absorvíveis , Carbocianinas/química , Corantes Fluorescentes/química , Alicerces Teciduais , Animais , Compostos de Bis-Trimetilamônio/química , Compostos de Bis-Trimetilamônio/farmacocinética , Carbocianinas/farmacocinética , Corantes Fluorescentes/farmacocinética , Gelatina/química , Teste de Materiais , Camundongos , Camundongos Nus , Imagem Óptica , Espectroscopia de Luz Próxima ao Infravermelho , Distribuição Tecidual , Engenharia Tecidual , Alicerces Teciduais/químicaRESUMO
Longitudinal monitoring of cell migration, division and differentiation is of paramount importance in cell-based medical treatment. However, currently available optical techniques for tracing cell growth and tissue development are limited in applications due to genetic modification, toxicity and inaccurate detection when utilizing the visible spectrum. We have developed lipophilic near-infrared (NIR) fluorophores with high optical properties and a low background signal that allows longitudinal monitoring of cell proliferation and differentiation. Intracellular labeling efficacy was highly dependent on the physicochemical properties of fluorophores such as lipophilicity, charge, polar surface area and rotational bonds. Among the series of NIR cyanine fluorophores, ESNF 13 showed high solubility in aqueous buffer, high membrane penetration, low cytotoxicity and a long-term signal maintainability with a high signal intensity. This study will guide tissue engineers in designing long-term cell trafficking agents with better physicochemical and optical properties.
Assuntos
Corantes Fluorescentes/química , Engenharia Tecidual/métodos , Animais , Compostos de Bis-Trimetilamônio/química , Compostos de Bis-Trimetilamônio/farmacocinética , Carbocianinas/química , Carbocianinas/farmacocinética , Diferenciação Celular , Linhagem Celular , Proliferação de Células , Condrócitos/citologia , Condrócitos/metabolismo , Corantes Fluorescentes/farmacocinética , Camundongos , Mioblastos/citologia , Mioblastos/metabolismo , Imagem Óptica , Solubilidade , Espectroscopia de Luz Próxima ao Infravermelho , Sus scrofaRESUMO
Optical fluorescence imaging with the right combination of imaging modality and targeted contrast agents offers tremendous improvement in intraoperative imaging and clinical output (i.e., image-guided cancer surgery). Therefore, it is of paramount importance to gain an in-depth knowledge in the design of targeted contrast agents to meet clinical requirements. Currently, there are several clinically approved contrast agents available; however, none perform optimally in vivo by providing optimum sensitivity, stability, specificity, and safety for target imaging, diagnosis, and therapy. In this review, we discuss basic design considerations for targeted contrast agents in terms of optical and physicochemical properties, biological and physiological interactions, and biodistribution and targeting.
