A hypoxia responsive nanoassembly for tumor specific oxygenation and enhanced sonodynamic therapy.
Biomaterials
; 275: 120822, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-34062419
ABSTRACT
The hypoxic tumor microenvironment (TME) and non-specific distribution of sonosensitizers are two major obstacles that limit practical applications of sonodynamic therapy (SDT) in combating tumors. Here we report a hypoxia-responsive nanovesicle (hMVs) as delivery vehicles of a sonosensitizer to enhance the efficacy of SDT via specific payload release and local oxygenation in the tumor. The nanovesicles are composed of densely packed manganese ferrite nanoparticles (MFNs) embedded in hypoxia-responsive amphiphilic polymer membranes. With δ-aminolevulinic acid (ALA) loaded in the hollow cavities, the hMVs could rapidly dissociate into discrete nanoparticles in the hypoxic TME to release the payload and induce the generation of reactive oxygen species (ROS) under ultrasound (US) radiation. Meanwhile, the released MFNs could catalytically generate O2 to overcome the hypoxic TME and thus enhance the efficacy of SDT. After treatment, the dissociated MFNs could be readily excreted from the body via renal clearance to reduce long term toxicity. In vitro and in vivo experiments displayed effective tumor inhibition via hMVs-mediated SDT, indicating the great potential of this unique nanoplatform in effective SDT by generating sufficient ROS in deep-seated hypoxic tumors that are not readily accessible by conventional photodynamic therapy.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nanopartículas
/
Hipóxia
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article