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Published on: January 8, 2016
Synthesis of Polystyrene-Based Cationic Nanomaterials with Pro-Oxidant Cytotoxic Activity on Etoposide-Resistant
Silvana Alfei1, Barbara Marengo2, Giulia Elda Valenti2
1Department of Pharmacy, University of Genoa, Viale Cembrano, 16148 Genoa, Italy.
Abstract:
Drug resistance is a multifactorial phenomenon that limits the action of antibiotics and chemotherapeutics. Therefore, it is essential to develop new therapeutic strategies capable of inducing cytotoxic effects circumventing chemoresistance. In this regard, the employment of natural and synthetic cationic peptides and polymers has given satisfactory results both in microbiology, as antibacterial agents, but also in the oncological field, resulting in effective treatment against several tumors, including neuroblastoma (NB). To this end, two polystyrene-based copolymers (P5, P7), containing primary ammonium groups, were herein synthetized and tested on etoposide-sensitive (HTLA-230) and etoposide-resistant (HTLA-ER) NB cells. Both copolymers were water-soluble and showed a positive surface charge due to nitrogen atoms, which resulted in protonation in the whole physiological pH range. Furthermore, P5 and P7 exhibited stability in solution, excellent buffer capacity, and nanosized particles, and they were able to reduce NB cell viability in a concentration-dependent way. Interestingly, a significant increase in reactive oxygen species (ROS) production was observed in both NB cell populations treated with P5 or P7, establishing for both copolymers an unequivocal correlation between cytotoxicity and ROS generation. Therefore, P5 and P7 could be promising template macromolecules for the development of new chemotherapeutic agents able to fight NB chemoresistance.
Insights
New cationic copolymers (P5, P7) show promise against drug-resistant neuroblastoma. These water-soluble polymers effectively reduce cancer cell viability by increasing reactive oxygen species (ROS), offering a potential new therapeutic strategy.
Area of Science:
- Biochemistry
- Materials Science
- Oncology
Background:
- Drug resistance limits antibiotic and chemotherapeutic efficacy.
- Developing novel strategies to overcome chemoresistance is crucial for effective treatment.
- Cationic peptides and polymers show potential in both antimicrobial and anticancer applications.
Purpose of the Study:
- To synthesize and evaluate two polystyrene-based copolymers (P5, P7) with primary ammonium groups.
- To assess the cytotoxic effects of P5 and P7 on etoposide-sensitive and etoposide-resistant neuroblastoma cells.
- To investigate the mechanism of cytotoxicity, specifically the role of reactive oxygen species (ROS).
Main Methods:
- Synthesis of polystyrene-based copolymers (P5, P7) with primary ammonium groups.
- Characterization of copolymer properties including solubility, surface charge, stability, buffer capacity, and particle size.
- In vitro testing of copolymer cytotoxicity on neuroblastoma cell lines (HTLA-230 and HTLA-ER).
- Measurement of intracellular reactive oxygen species (ROS) levels in treated cells.
Main Results:
- Both P5 and P7 copolymers were water-soluble, stable, and formed nanosized particles.
- Copolymers exhibited positive surface charge and excellent buffer capacity across physiological pH.
- P5 and P7 demonstrated concentration-dependent reduction in neuroblastoma cell viability.
- A significant increase in ROS production was observed in cells treated with P5 or P7, correlating with cytotoxicity.
Conclusions:
- The synthesized copolymers P5 and P7 are effective in reducing neuroblastoma cell viability.
- Cytotoxicity of P5 and P7 is mediated by increased reactive oxygen species (ROS) generation.
- These copolymers represent promising macromolecular platforms for developing novel agents against chemoresistant neuroblastoma.
