Photoactive Parietin-loaded nanocarriers as an efficient therapeutic platform against triple-negative breast cancer

被引:6
|
作者
Ayoub, Abdallah M. [1 ,2 ]
Abdelsalam, Ahmed M. [1 ,3 ]
Schulze, Jan [1 ]
Amin, Muhammad U. [1 ]
Engelhardt, Konrad [1 ]
Wojcik, Matthias [1 ]
Librizzi, Damiano [4 ]
Yousefi, Behrooz H. [4 ]
Nasrullah, Usman [5 ]
Pfeilschifter, Josef [5 ]
Bakowsky, Udo [1 ]
Preis, Eduard [1 ]
机构
[1] Univ Marburg, Dept Pharmaceut & Biopharmaceut, Marburg, Germany
[2] Zagazig Univ, Fac Pharm, Dept Pharmaceut, Ind Pharm, Zagazig, Egypt
[3] Al Azhar Univ, Fac Pharm, Dept Pharmaceut, Ind Pharm, Assiut, Egypt
[4] Univ Marburg, Ctr Tumor Biol & Immunol ZTI, Dept Nucl Med, Core Facil Mol Imaging, Marburg, Germany
[5] Goethe Univ Frankfurt, Univ Hosp Frankfurt, Inst Gen Pharmacol & Toxicol, Frankfurt, Germany
关键词
Photodynamic therapy; Antiangiogenesis; Reactive oxygen species; PLGA nanoparticles; Physcion; MDA-MB-231; CAM model; DRUG-DELIVERY-SYSTEMS; PHOTODYNAMIC THERAPY; IN-VIVO; PLGA NANOPARTICLES; CHORIOALLANTOIC MEMBRANE; CELLS; INACTIVATION; PHTHALOCYANINE; DEGRADATION; FORMULATION;
D O I
10.1016/j.ijpharm.2023.123217
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The application of photodynamic therapy has become more and more important in combating cancer. However, the high lipophilic nature of most photosensitizers limits their parenteral administration and leads to aggregation in the biological environment. To resolve this problem and deliver a photoactive form, the natural photosensitizer parietin (PTN) was encapsulated in poly(lactic-co-glycolic acid) nanoparticles (PTN NPs) by emulsification diffusion method. PTN NPs displayed a size of 193.70 nm and 157.31 nm, characterized by dynamic light scattering and atomic force microscopy, respectively. As the photoactivity of parietin is essential for therapy, the quantum yield of PTN NPs and the in vitro release were assessed. The antiproliferative activity, the intracellular generation of reactive oxygen species, mitochondrial potential depolarization, and lysosomal membrane permeabilization were evaluated in triple-negative breast cancer cells (MDA-MB-231 cells). At the same time, confocal laser scanning microscopy (CLSM) and flow cytometry were used to investigate the cellular uptake profile. In addition, the chorioallantoic membrane (CAM) was employed to evaluate the antiangiogenic effect microscopically. The spherical monomodal PTN NPs show a quantum yield of 0.4. The biological assessment on MDA-MB-231 cells revealed that free PTN and PTN NPs inhibited cell proliferation with IC50 of 0.95 & mu;M and 1.9 & mu;M at 6 J/cm2, respectively, and this can be attributed to the intracellular uptake profile as proved by flow cytometry. Eventually, the CAM study illustrated that PTN NPs could reduce the number of angiogenic blood vessels and disrupt the vitality of xenografted tumors. In conclusion, PTN NPs are a promising anticancer strategy in vitro and might be a tool for fighting cancer in vivo.
引用
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页数:20
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