Engineered anti-HER2 drug delivery nanosystems for the treatment of breast cancer

Abstract

Breast cancer stands as the primary cancer affecting women and the second most prevalent cause of cancer-related fatalities in developed nations. Consequently, there is a pressing demand for the advancement of therapeutic strategies that can be seamlessly integrated into clinical applications. We investigated the effectiveness of an encapsulation and decoration strategy employing biodegradable and biocompatible carriers together with 3D collagen-based culture models. Envisioning the use of nano delivery systems for localized regional release, we explored the feasibility of a light-controlled drug release, assisted by optical fibers. PLGA nanoparticles loaded or decorated with trastuzumab (TZ) were synthesized via a double emulsion protocol and characterized by dynamic light scattering, surface plasmon resonance, transmission electron microscopy, atomic force microscopy, and Fourier transform infrared spectroscopy. In vitro biological evaluation was then performed on HER2-positive breast cancer cell line BT-474, examining the effect of nanoformulations on cell viability in 2D and 3D collagen scaffold culture models. Cell cycle, apoptosis, cell morphology and distribution and protein expression were analyzed. Finally, a core-offset optical fiber was fabricated and particles release was studied in vitro using light in batch and microfluidic tests. The nanoparticles displayed uniform and spherical shape, maintaining stability in DMEM for up to seven days. The successful immobilization of TZ was verified. In vitro trials with BT-474 cells in 2D and 3D models revealed that poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulated with TZ demonstrated similar or superior biological activity compared to free TZ. Notably, PLGA functionalized with TZ both internally and on the surface exhibited the highest effectiveness in terms of cell viability, increase of apoptosis markers, and inducing cell quiescence. This affirms the pivotal role of PLGA nanoparticles in preserving the integrity of TZ and enhancing its targeted delivery. Furthermore, we propose a breakthrough fiber-optic technology for the less invasive local delivery of PLGA-based nanocarriers that can be effectively used in clinical practice. In conclusion our studies lay the foundation for future advancements in alternative therapeutic tools for localized breast cancer treatment. The integration of advanced carriers, optical fibers, and microfluidics opens up new possibilities for innovative and targeted therapeutic approaches.