RESUMEN
Targeted drug delivery to malignant bone lesions remains a challenging task in the treatment of bone tumors. In this article, we reported a naturally occurring phytic acid (PA) with both bone-targeting capability and anticancer activity. The PA-capped platinum nanoparticles showed high affinity to hydroxyapatite in vitro and in vivo, and maintained both the inherent anticancer ability of PA and photothermal effect of platinum nanoparticles. PA-capped nanoparticles displayed a 4-fold higher accumulation in the osteolytic lesions than sodium citrate-templated ones, and efficiently inhibited bone tumor growth and the tumor associated-osteolysis upon exposure to a near-infrared light. This study provides a novel and efficient strategy to prepare bone-targeted nanoparticles with inherent anticancer activity for combination therapy of malignant bone tumors.
Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Óseas/terapia , Nanopartículas/uso terapéutico , Ácido Fítico/uso terapéutico , Platino (Metal)/uso terapéutico , Animales , Neoplasias Óseas/patología , Línea Celular Tumoral , Terapia Combinada/métodos , Sistemas de Liberación de Medicamentos/métodos , Humanos , Hipertermia Inducida/métodos , Masculino , Ratones , Ratones Endogámicos BALB C , Células 3T3 NIHRESUMEN
Malignant bone tumors associated with aggressive osteolysis are currently hard to be cured by the clinical strategies. Nevertheless, nanomedicine might provide a promising therapeutic opportunity. Here, we developed a multifunctional melanin-like nanoparticle for bone-targeted chemo-photothermal treatment of malignant bone tumors. The particle was originally fabricated from alendronate-conjugated polydopamine nanoparticle (PDA-ALN) that exhibited excellent photothermal effect and high affinity to hydroxyapatite. PDA/Fe-ALN significantly enhanced the magnetic resonance contrast of the bone tumors in vivo, suggesting that more PDA-ALN accumulated at the osteolytic bone lesions in the tumors compared with the non-targeting PDA. Chemodrug SN38 was efficiently loaded on PDA-ALN, and the drug release could be triggered by near-infrared irradiation and acidic stimulus. Finally, the combined chemo-photothermal therapy efficiently suppressed the growth of bone tumors and reduced the osteolytic damage of bones at a mild temperature around 43⯰C. This study provides an efficient and robust nanotherapeutics for the treatment of malignant bone tumors.
Asunto(s)
Neoplasias Óseas/terapia , Melaninas/química , Nanopartículas/química , Osteólisis/tratamiento farmacológico , Alendronato/química , Animales , Antineoplásicos/administración & dosificación , Neoplasias Óseas/diagnóstico por imagen , Huesos/metabolismo , Células Cultivadas , Terapia Combinada , Durapatita/metabolismo , Xenoinjertos , Hipertermia Inducida , Indoles/química , Rayos Infrarrojos , Irinotecán/administración & dosificación , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fototerapia/métodos , Polímeros/química , Distribución TisularRESUMEN
The treatment of bone tumors is a challenging problem due to the inefficient delivery of therapeutics to bone and the bone microenvironment-associated tumor resistance to chemo- and radiotherapy. Here, we developed a bone-targeted nanoparticle, aspartate octapeptide-modified dendritic platinum-copper alloy nanoparticle (Asp-DPCN), for photothermal therapy (PTT) of bone tumors. Asp-DPCN showed much higher affinity toward hydroxyapatite and bone fragments than the non-targeted DPCN in vitro. Furthermore, Asp-DPCN accumulated more efficiently around bone tumors in vivo, and resulted in a higher temperature in bone tumors during PTT. Finally, Asp-DPCN-mediated PTT not only efficiently depressed the tumor growth but also significantly reduced the osteoclastic bone destruction. Our study developed a promising therapeutic approach for the treatment of bone tumors.
Asunto(s)
Neoplasias Óseas/metabolismo , Neoplasias Óseas/terapia , Hipertermia Inducida/métodos , Nanopartículas del Metal/uso terapéutico , Terapia Molecular Dirigida/métodos , Oligopéptidos/farmacocinética , Fototerapia/métodos , Animales , Neoplasias Óseas/patología , Línea Celular Tumoral , Masculino , Nanopartículas del Metal/administración & dosificación , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Nanocápsulas/administración & dosificación , Nanocápsulas/uso terapéutico , Oligopéptidos/administración & dosificación , Resultado del TratamientoRESUMEN
Bone metastasis is a frequent and fatal complication of cancer that lacks effective clinical treatment. Photothermal therapy represents a new strategy for the destruction of multiple cancers. In this study, trifolium-like platinum nanoparticles (TPNs) with small size and excellent photothermal conversion property are prepared via a facile and green method. TPNs show minimal cytotoxicity on normal cell lines and kill cancer cells upon exposure to a near-infrared light. These nanoparticles effectively inhibit tumor growth and prevent osteolysis in a bone metastasis model. This study offers a promising strategy in the treatment of bone metastasis.