Codelivery of methotrexate and silibinin by niosome nanoparticles for enhanced chemotherapy of CT26 colon cancer cells.
Masoumeh Sharifi-AzadMasumeh Kaveh ZenjanabMohammad ShahpouriMohammad Amin Adili-AghdamMarziyeh FathiRana Jahanban-EsfahlanPublished in: Biomedical materials (Bristol, England) (2024)
Colon cancer (CC) is one of the most prevalent cancers in the world, and chemotherapy is widely applied to combat it. However, chemotherapy drugs have severe side effects and emergence of multi drug resistance (MDR) is common. This bottleneck can be overcome by niosome nanocarriers that minimize drug dose/toxicity meanwhile allow co-loading of incompatible drugs for combination therapy. In this research, silibinin (Sil) as a hydrophobic drug was loaded into the lipophilic part, and methotrexate (MTX) into the hydrophilic part of niosome by the thin film hydration (TFH) method to form Nio@MS NPs for CT26 colon cancer therapy in vitro . Our results indicated synthesis of ideal niosome nanoparticles (NPs) with spherical morphology, size of ∼100 nm, and a zeta potential of -10 mV. The IC 50 value for Nio@MS was determined ∼2.6 µg ml -1 , which was significantly lower than MTX-Sil (∼6.86 µg ml -1 ), Sil (18.46 µg ml -1 ), and MTX (9.8 µg ml -1 ). Further, Nio@MS significantly reduced cell adhesion density, promoted apoptosis and increased gene expression level of caspase 3 and BAX while promoted significant downregulation of BCL2. In conclusion, the design and application of niosome to co-administer Sil and MTX can increase the drugs cytotoxicity, reduce their dose and improve anti-cancer potential by combating MDR.
Keyphrases
- cancer therapy
- combination therapy
- mass spectrometry
- drug delivery
- gene expression
- multiple sclerosis
- ms ms
- cell adhesion
- locally advanced
- drug induced
- multidrug resistant
- oxidative stress
- liquid chromatography
- computed tomography
- dual energy
- cell death
- image quality
- high dose
- induced apoptosis
- contrast enhanced
- endoplasmic reticulum stress
- dna methylation
- positron emission tomography
- magnetic resonance imaging
- cell proliferation
- squamous cell carcinoma
- human health
- signaling pathway
- oxide nanoparticles
- risk assessment
- adverse drug
- low dose
- emergency department
- radiation therapy
- climate change
- solid phase extraction