Preparation and Characterization of Stattic-Loaded Albumin Nanoparticles for Antimetastatic Cancer Treatment

Abstract

Stattic offers a unique inhibitory effect on the STAT3 signaling pathway, a crucial mechanism in the progression of metastatic cancer. However, the development of Stattic has been impeded by its hydrophobicity and lack of specificity. To overcome these limitations, encapsulation of Stattic with polymeric micelles was previously attempted, which led to a significant increase in the potency of Stattic on breast cancer cell lines. The presence of albumin was believed to contribute to such enhancement, as the protein corona layer formation helps to retain the micellar structure before eventual uptake by the cells. Moreover, a previous study had reported the unique affinity of Stattic towards albumin molecule. This study aimed to explore the integration of Stattic in albumin-based nanoparticles and to assess the in vitro effects. Albumin/Stattic nanoparticles were prepared by crosslinking with glutaraldehyde. The yielded nanoparticles were 150.0 ± 6.6 nm in size, with ~53% entrapment efficiency. The cumulative release of Stattic in a tumoric acidic environment (pH 5.3; 59%) was 2.6-fold more than neutral environment (pH 7.4; 23%). In blood plasma, 7% cumulative release was observed. The mathematical modeling of the release kinetics revealed that the albumin/Stattic nanoparticles in phosphate buffer saline and plasma followed Korsmeyer-Peppas and Higuchi model, respectively. Among the two cell lines tested, metastatic MDA-MB-231 cells were more sensitive to entrapment of Stattic with albumin nanoparticles, as the IC50 value decreased by 2.5-fold compared to free Stattic. This study reports the formation of low immunogenic and cost-efficient albumin nanoparticles to improve the delivery of Stattic.