A glucose-targeted mixed micellar formulation outperforms Genexol in breast cancer cells
Marcela A Moretton1, Ezequiel Bernabeu1, Estefanía Grotz1
1Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Tecnología Farmacéutica I, Buenos Aires, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.
Abstract:
Breast cancer represents the top cancer among women, accounting 521.000 deaths per year. Development of targeted nanomedicines to breast cancer tissues represents a milestone to reduce chemotherapy side effects. Taking advantage of the over-expression of glucose (Glu) membrane transporters in breast cancer cells, we aim to expand the potential of a paclitaxel (PTX)-loaded mixed micellar formulation based on polyvinyl caprolactam-polyvinylacetate-polyethylene glycol graft copolymer (Soluplus®) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) by its surface decoration with Glu moieties. The glycopolymer (Soluplus(Glu)) was obtained by microwave-assisted ring opening reaction of δ-gluconolactone initiated by Soluplus®. The glycosylation was confirmed by 1H NMR and by agglutination assays employing Concanavalin A. The hydrodynamic diameter of Soluplus(Glu) micelles was characterized by dynamic light scattering (100.3±3.8nm) as well as the critical micellar concentration value (0.0151% w/v). Then, a mixed micelle formulation employing Soluplus®, Soluplus(Glu) and TPGS (3:1:1wt ratio) loaded with PTX (4mg/mL) was developed as a multifunctional nanocarrier. Its in vitro anticancer performance in MCF-7 (1.6-fold) and MDA-MB-231 (14.1-fold) was significantly enhanced (p<0.05) versus the unique commercially available micellar-based PTX-nanoformulation (Genexol®). Furthermore, the in vitro PTX cellular uptake assays revealed that the drug intracellular/cell content was significantly (p<0.05) higher for the Glu-containing mixed micelles versus Genexol® after 6h of incubation with MCF-7 (30.5-fold) and MDA-MB-231 (5-fold). Overall, results confirmed the potential of our Glu-decorated mixed colloidal formulation as an intelligent nanocarrier for PTX-targeted breast cancer chemotherapy.
Insights
Targeted breast cancer chemotherapy was improved using glucose-decorated mixed micelles. This novel nanocarrier enhances paclitaxel delivery and efficacy, reducing side effects for improved patient outcomes.
Area of Science:
- Nanomedicine
- Polymer Chemistry
- Oncology
Background:
- Breast cancer is a leading cause of death in women, necessitating improved chemotherapy with reduced side effects.
- Targeted nanomedicines offer a promising strategy to deliver chemotherapy agents specifically to cancer tissues.
- Over-expression of glucose transporters in breast cancer cells presents a target for selective drug delivery.
Purpose of the Study:
- To develop a paclitaxel-loaded mixed micellar formulation surface-decorated with glucose (Glu) moieties for targeted breast cancer therapy.
- To enhance the efficacy and cellular uptake of paclitaxel (PTX) in breast cancer cells using a novel nanocarrier.
Main Methods:
- Synthesis of a glycopolymer (Soluplus(Glu)) via microwave-assisted ring opening of δ-gluconolactone initiated by Soluplus®.
- Characterization of Soluplus(Glu) micelles using 1H NMR, agglutination assays, dynamic light scattering, and critical micellar concentration determination.
- Development and evaluation of a PTX-loaded mixed micelle formulation (Soluplus®, Soluplus(Glu), TPGS) for in vitro anticancer performance and cellular uptake studies.
Main Results:
- The synthesized glycopolymer and its micelles were confirmed by spectroscopic and biophysical methods.
- The PTX-loaded mixed micelles demonstrated significantly enhanced in vitro anticancer activity against MCF-7 and MDA-MB-231 cells compared to Genexol®.
- In vitro cellular uptake studies showed a significant increase in intracellular paclitaxel content for the glucose-decorated micelles in both cell lines.
Conclusions:
- Glucose-decorated mixed micelles represent an effective nanocarrier for paclitaxel delivery in breast cancer.
- The targeted approach enhances drug efficacy and cellular uptake, indicating potential for improved breast cancer chemotherapy.
- This intelligent nanocarrier formulation holds promise for reducing chemotherapy side effects and improving treatment outcomes.
