A multifunctional bioresponsive and fluorescent active nanogel composite for breast cancer therapy and bioimaging

Abstract

Bio-responsive nanocomposites with facile fabrication and rational design are of great importance in the diagnosis and treatment of cancer. Herein, the combination of bioimaging due to the presence of QD and controlled drug delivery via nanogel was employed for cancer treatment. To this aim, we fabricated a traceable and bioresponsive fluorescent active nanogel composite by integrating creatinine-functionalized carbon dots (QD) into a lecithin-inulin nanogel. Subsequently, PEGylation and integration of herceptin on the nanogel were carried out to improve the biofate and its ability to target HER2-positive breast cancer. The assessment of cellular uptake demonstrated that this nanogel was effectively internalized by SK-BR-3 cells and the production of reactive oxygen species was significantly boosted. Moreover, the nanogel composite led to high expression of P53 and Bax genes along with a low expression of Bcl-2 gene (as promotors of the apoptosis signaling pathway). The cellular uptake of herceptin was enhanced. It led to inhibiting the proliferation of the breast cancer cells as well as the reduction of viability of SK-BR-3 cancer cells (HER-2 positive) compared with MDA-MB-231 cells (triple-negative). The intraperitoneal injection of the developed formulation to MCF-7 breast cancer cell-bearing BALB/c mice supported the observation of tumor growth inhibition. Overall, herceptin-adorned PEGylated lecithin-inulin nanogel composite can be a promising theranostic candidate for targeting HER-2-positive breast cancer. Graphical Abstract: [Figure not available: see fulltext.].