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2000
Volume 22, Issue 6
  • ISSN: 1567-2018
  • E-ISSN: 1875-5704

Abstract

Background

The clinical efficiency of photodynamic therapy (PDT) in combination with chemotherapy has proven to be a promising strategy for tumor treatment, yet is restricted by the high glutathione (GSH) concentration at the tumor site and nonspecific drug targeting.

Objective

The goal of the current research was to create a biocompatible GSH-depleting and tumor-targeting nanoparticle (denoted as DOX/CA@PCN-224@HA) for the combined photodynamic and chemo photo-chemo) therapy.

Methods

The nanoparticles were characterized by transmission electron microscopy (TEM). A UV-vis spectrophotometer was used to measure the drug loading efficiency (DE) and encapsulation efficiency (EE). The GSH-depleting ability was measured using Ellman's test. Confocal laser scan microscopy (CLSM) was used to assess the cellular uptake. MTT was adopted to evaluate the cytotoxicity of DOX/CA@PCN-224@HA against 4T1 cells.

Results

The altered PCN-224 showed excellent monodispersing with a dimension of approximately 193 nm ± 2 nm in length and 79 nm ± 3 nm in width. The larger and spindle grid-like structure of PCN-224 obtains better dual-drug loading ability (DOX: 20.58% ± 2.60%, CA: 21.81% ± 1.98%) compared with other spherical PCN-224 nanoparticles. The ultimate cumulative drug release rates with hyaluronidase (HAase) were 74% ± 1% (DOX) and 45% ± 2% (CA) after 72 h. DOX/CA@PCN-224@HA showed GSH-consuming capability, which could improve the PDT effect. The drug-loaded nanoparticles could accurately target 4T1 cells through biological evaluations. Moreover, the released DOX and CA display cooperative effects on 4T1 cells . DOX/CA@PCN-224@HA nanoparticles showed inhibition against 4T1 cells with an IC value of 2.71 μg mL-1.

Conclusion

This nanosystem displays great potential for tumor-targeted enhanced (photo-chemo) therapy.

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An Enzyme-responsive Porphyrin Metal-organic Framework Nanosystem for Targeted and Enhanced Synergistic Cancer Photo-chemo Therapy
Curr. Drug Deliv. 22, 784 (2025); https://doi.org/10.2174/0115672018286563240223072702
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  • Article Type:     Research Article
Keyword(s): combined therapeutic; metal-organic framework; Photodynamic therapy; tumor targeting, PDT, FBS

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