Calcium-bisphosphonate Nanoparticle Platform as a Prolonged Nanodrug and Bone-Targeted Delivery System for Bone Diseases and Cancers.
ACS Appl Bio Mater
; 4(3): 2490-2501, 2021 03 15.
Article
em En
| MEDLINE
| ID: mdl-35014367
ABSTRACT
Bone and bone-related diseases are the major cause of mobility hindrance and mortality in humans and there is no effective and safe treatment for most of them, especially, for bone and bone metastatic cancers. Bisphosphonates (BPs) are a group of small-molecule drugs for treating osteoporosis and bone cancers but have a very short half-life in circulation, requiring high doses and long-term repeat use that can cause severe side effects. Previous attempts of using nanoparticles to deliver BPs have issues of drug loading capacity and endosome escape/drug release. The present study reports the direct synthesis of BP nanoparticles by precipitating bone-favorable calcium ions and a third-generation BP, risedronate (Ca-RISNPs), to achieve high drug loading, endosomal release, and strong bone-targeting properties. The Ca-RISNPs are monodispersed with high stability at physiological pH but readily dissociate at endosomal pH conditions. They demonstrate strong penetration ability and uniform distribution in human bone and cartilage tissues and the superior drug and DNA (plasmid and oligo double strand DNA) delivery capacity in bone cells. These NPs also exhibit high specificity in killing tumor-associated macrophages (TAMs) and inhibit TAM-induced tumor cell migration. Collectively, our data indicate that this BP nanodrug platform has a great potential in managing bone-related diseases and cancers as a prolonged BP nanodrug and simultaneously as the bone-targeted drug delivery system.
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Base de dados:
MEDLINE
Assunto principal:
Materiais Biocompatíveis
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Doenças Ósseas
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Neoplasias Ósseas
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Doxorrubicina
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Sistemas de Liberação de Medicamentos
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Antibióticos Antineoplásicos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article