Title:An Enzyme-responsive Porphyrin Metal-organic Framework Nanosystem for Targeted and Enhanced Synergistic Cancer Photo-chemo Therapy
Volume: 21
Author(s): Mengqi Yi, Yangxin Lin, Yuyang Li, Bei Xiong, Yunhan Huang, Wei Guo and Bo Lu*
Affiliation:
- School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, 430070, China
Keywords:
Photodynamic therapy, metal-organic framework, combined therapeutic, tumor targeting.
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 in vitro.
DOX/CA@PCN-224@HA nanoparticles showed inhibition against 4T1 cells with an IC50 value of
2.71 μg mL-1.
Conclusion: This nanosystem displays great potential for tumor-targeted enhanced (photo-chemo)
therapy.
