Tandem activated photodynamic and chemotherapy: Using pH-Sensitive nanosystems to realize different tumour distributions of photosensitizer/prodrug for amplified combination therapy.
Biomaterials
; 219: 119393, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-31382206
ABSTRACT
Photodynamic therapy (PDT) combined with hypoxia-activated prodrugs to overcome hypoxia environment has been recently explored as a promising clinical modality for cancer therapy. Nevertheless, delivering these two therapeutic agents together to different tumour areas that possess a number of biological barriers remains a considerable challenge. Herein, we used the semiconducting polyelectrolyte-based zwitterionic photosensitizer (PFNS) to modify the surface of upconversion nanoparticles (NPs) and prepare near-infrared (NIR) light-responsive PDT agents (UCNP@PFNS). A pH-sensitive Mn-Ca3(PO4)2 (MnCaP) layer was further coated onto UCNP@PFNS with the hypoxia-activated prodrug AQ4N incorporated inside. The final nanocomposites exhibited a diameter of 73â¯nm with high stability in the blood and a remarkably enhanced permeability and retention (EPR) effect in tumours. Importantly, when these nanoparticles reached the tumour site, the acidic tumour microenvironment (pH 6.5-6.8) decomposed the MnCaP layer, releasing both UCNP@PFNS (30â¯nm) and AQ4N. The relatively small size of UCNP@PFNS and AQ4N satisfied the different distribution requirements in tumour and achieved a high therapeutic effect, thereby reaching an inhibition rate of as high as 83%. In addition, Mn2+ ions can be released during the decomposition of CaP, leading to a significantly increased magnetic resonance (MR) signal in the tumour site. Overall, we report a nanoparticle guided by MRI and fluorescence imaging possesses of tandem active pattern of PDT and chemotherapy, which is promising for future clinical diagnosis and treatment.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fotoquimioterapia
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Pró-Fármacos
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Fármacos Fotossensibilizantes
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Nanocompostos
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Biomaterials
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China