Evaluation of Estrone Liposomes using Microfluidics for Breast Cancer Therapy

Abstract

Breast cancer, the predominant and frequently recurring cancer in women on a global scale, presents challenges to traditional chemotherapy methods. This is primarily due to issues such as systemic toxicity, low solubility, irregular biodistribution, and poor tumor site localization. Nanocarriers provide a solution by encapsulating the agent to safeguard healthy cells and minimize side effects. However, enhancing their effectiveness remains an obstacle. To overcome these challenges, a cell culture model that more accurately represents the in vivo environment is crucial for assessing various nano-based drug delivery systems (DDSs), including liposomes. Microfluidic devices provide innovative platforms for in vitro drug assessments by mimicking the in vivo conditions. This study developed a microfluidic platform to investigate estrone (ES) liposomes as DDSs for breast cancer therapy under static and dynamic conditions. While static conditions showed the influence of attaching ES targeting moiety on cellular uptake, an in vitro study under flow conditions demonstrated that higher shear stresses significantly enhanced the uptake of ES-conjugated liposomes by estrogen receptor (ER)-positive MCF-7 cells compared to static conditions. This increased uptake could be due to receptor-mediated endocytosis, shear induced permeabilization of the cell membrane, or a higher collision rate between liposomes and cells at high shear stresses. This highlights the synergistic effects of receptor-mediated targeting and fluid shear stress in an in vivo-like environment. These findings advance the understanding of ES-conjugated liposomes as efficient DDSs for breast cancer treatment, emphasizing potential clinical applications and enhancing the in vitro-in vivo correlation. Ongoing work will explore additional factors influencing cellular uptake within microchannels, including liposome size and ES concentration. Future investigations will also involve optimizing multiple channel geometries to study the effect of flow variations on liposomal cellular uptake, integrating multiple cell lines within a microfluidic chip, and introducing external triggering mechanisms, such as ultrasound.