RESUMO
Carrier-free nanotheranostics directly assembled by using clinically used photosensitizers and chemotherapeutic drugs are a promising alternative to tumor theranostics. However, the weak interaction-driven assembly still suffers from low structural stability against disintegration, lack of targeting specificity, and poor stimulus-responsive property. Moreover, almost all exogenous ligands possess no therapeutic effect. Enlightened by the concept of metal-organic frameworks, we developed a novel self-recognizing metal-coordinated nanotheranostic agent by the coordination-driven co-assembly of photosensitizer indocyanine green (ICG) and chemo-drug methotrexate (MTX, also served as a specific "targeting ligand" towards folate receptors), in which ferric (FeIII) ions acted as a bridge to tightly associate ICG with MTX. Such carrier-free metal-coordinated nanotheranostics with high dual-drug payload (â¼94 wt%) not only possessed excellent structural and physiological stability, but also exhibited prolonged blood circulation. In addition, the nanotheranostics could achieve the targeted on-demand drug release by both stimuli of internal lysosomal acidity and external near-infrared laser. More importantly, the nanotheranostics could self-recognize the cancer cells and selectively target the tumors, and therefore they decreased toxicity to normal tissues and organs. Consequently, the nanotheranostics showed strongly synergistic potency for tumor photo-chemotherapy under the precise guidance of magnetic resonance/photoacoustic/fluorescence imaging, thereby achieving highly effective tumor curing efficiency. Considering that ICG and bi-functional MTX are approved by the Food and Drug Administration, and FeIII ions have high biosafety, the self-recognizing and stimulus-responsive carrier-free metal-coordinated nanotheranostics may hold potential applications in tumor theranostics.
Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Verde de Indocianina/farmacologia , Metotrexato/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Fototerapia , Nanomedicina Teranóstica , Animais , Antimetabólitos Antineoplásicos/síntese química , Antimetabólitos Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Verde de Indocianina/síntese química , Verde de Indocianina/química , Imageamento por Ressonância Magnética , Metotrexato/síntese química , Metotrexato/química , Camundongos , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Imagem Óptica , Tamanho da Partícula , Técnicas Fotoacústicas , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Propriedades de SuperfícieRESUMO
OBJECTIVE: To find out the essence of the traditional Chinese medicine properties from detecting the rats' monoamine neurotransmitter after given different traditional Chinese drug. METHOD: The property of rhizome curcumae and radix curcumae is opposite, they were given to rats respectively for one month. Next, HPLC-ECD method was used to detect the rats' monoamine neurotransmitter in different encephalic region. RESULT: Rhizome curcumae can raise the rats' monoamine neurotransmitter, but radix curcumae inhibits the rats' monoamine neurotransmitter. CONCLUSION: There are correlations between the traditional Chinese medicine properties and monoamine neurotransmitter.