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Cytotoxic, Apoptotic and Genotoxic Effects of Lipid-Based and Polymeric Nano Micelles, an In Vitro Evaluation
Fatemeh Bahadori1, Abdurrahim Kocyigit2, Hayat Onyuksel3
1Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Bezmialem Vakif University, Fatih, Istanbul 34093, Turkey. fatemehbahadori@hotmail.com.
Abstract:
Self-assembly systems (SAS) mainly consist of micelles, and liposomes are the classes of Nano Drug Delivery Systems with superior properties compared to traditional therapeutics in targeting cancer tumors. All commercially available nano-formulations of chemotherapeutics currently consist of SAS. According to our knowledge, a specific toxicity comparison based on material differences has not yet been performed. The purpose of this study was to evaluate and compare the toxicity of two SAS consisting of Sterically Stabilized Micelles (SSM) made of a lipid-based amphiphilic distearoyl-sn-glycero-phosphatidylethanolamine-polyethylene glycol (PEG)-2000 and a polymeric micelle (PM) consisting of Y-shape amphiphilic block copolymer, synthesized using poly ε-caprolactone and PEG. The mechanism of cytotoxicity and genotoxicity of micelles on L-929 healthy mouse fibroblast cells was assessed using Sulforhodamine-B, WST-1, Acridine Orange/Ethidium Bromide and alkaline single-cell gel electrophoresis assays. Results showed that SSM in conc. of 40 mg/mL shows very low cytotoxicity at the end of 24, 48 and 72 h. The DNA damage caused by SSM was much lower than PM while the latter one showed significant toxicity by causing apoptosis with the ED50 value of 3 mg/mL. While the DNA damage caused by SSM was ignorable, some DNA chain breaks were detected on cells treated with PM.
Insights
Sterically stabilized micelles (SSM) show low cytotoxicity and minimal DNA damage compared to polymeric micelles (PM). This study highlights material differences in nano drug delivery systems for safer cancer therapeutics.
Area of Science:
- Nanotechnology
- Materials Science
- Biomedical Engineering
Background:
- Self-assembly systems (SAS), including micelles and liposomes, are key Nano Drug Delivery Systems (NDDS) for cancer therapeutics.
- Commercially available nano-chemotherapeutics utilize SAS, yet material-specific toxicity comparisons are lacking.
Purpose of the Study:
- To evaluate and compare the cytotoxicity and genotoxicity of two distinct SAS: Sterically Stabilized Micelles (SSM) and Polymeric Micelles (PM).
- To assess the impact of material composition on the safety profile of these nano drug delivery systems.
Main Methods:
- Utilized L-929 healthy mouse fibroblast cells for toxicity assessments.
- Employed Sulforhodamine-B, WST-1, Acridine Orange/Ethidium Bromide staining, and alkaline single-cell gel electrophoresis assays.
- Investigated cytotoxicity and genotoxicity mechanisms, including apoptosis and DNA damage.
Main Results:
- SSM exhibited very low cytotoxicity even at 40 mg/mL over 72 hours.
- PM demonstrated significant toxicity, inducing apoptosis with an ED50 of 3 mg/mL.
- SSM caused negligible DNA damage, whereas PM induced detectable DNA chain breaks.
Conclusions:
- SSM presents a safer alternative to PM for Nano Drug Delivery Systems due to its superior biocompatibility and reduced genotoxicity.
- Material choice in SAS is critical for developing effective and safe cancer therapeutics.
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