| Autor: |
Giri D; Biochemistry, Molecular Endocrinology and Reproductive Physiology Laboratory, Department of Human Physiology, Vidyasagar University, Midnapore, West Bengal, India, 721102.; Department of Physiology, Ghatal Rabindra Satabarsiki Mahavidyalaya, Ghatal, Paschim Medinipur, West Bengal, India, 721212., Dey SK; Biochemistry, Molecular Endocrinology and Reproductive Physiology Laboratory, Department of Human Physiology, Vidyasagar University, Midnapore, West Bengal, India, 721102., Manna S; Biochemistry, Molecular Endocrinology and Reproductive Physiology Laboratory, Department of Human Physiology, Vidyasagar University, Midnapore, West Bengal, India, 721102., Das Chaudhuri A; Biochemistry, Molecular Endocrinology and Reproductive Physiology Laboratory, Department of Human Physiology, Vidyasagar University, Midnapore, West Bengal, India, 721102., Mahata R; Biochemistry, Molecular Endocrinology and Reproductive Physiology Laboratory, Department of Human Physiology, Vidyasagar University, Midnapore, West Bengal, India, 721102., Pradhan A; Biochemistry, Molecular Endocrinology and Reproductive Physiology Laboratory, Department of Human Physiology, Vidyasagar University, Midnapore, West Bengal, India, 721102., Roy T; Biochemistry, Molecular Endocrinology and Reproductive Physiology Laboratory, Department of Human Physiology, Vidyasagar University, Midnapore, West Bengal, India, 721102., Jana K; Division of Molecular Medicine, Bose Institute, P1/12 CIT scheme VIIM, Kolkata, West Bengal, India, 700054., Das S; Department of Surgery, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612, United States., Roy S; Department of Chemistry and Chemical Technology, Vidyasagar University, Midnapore, West Bengal, India, 721102., Maiti Choudhury S; Biochemistry, Molecular Endocrinology and Reproductive Physiology Laboratory, Department of Human Physiology, Vidyasagar University, Midnapore, West Bengal, India, 721102. |
| Abstrakt: |
Triple-negative breast cancer (TNBC) is recognized as a major aggressive subtype of breast cancer due to its expeditious worsening growth, extensive metastatic capability, and recalcitrance to standard current treatments. Hesperetin (HSP), a natural bioflavonoid from citrus fruits, demonstrates pronounced anticancer efficacy, but its hydrophobicity limits its clinical development. The present study reports the fabrication of a biocompatible and pH-responsive transferrin (TF) receptor-targeted HSP-loaded poly(lactic- co -glycolic acid) (PLGA) nanobioconjugate (PLGA-HSP-TF NPs) and the exploration of its in vitro and in vivo antineoplastic potential. PLGA nanoparticles (NPs), PLGA-HSP NPs, and PLGA-HSP-TF NPs were synthesized and characterized by DLS, FTIR, FE-SEM, and 1 H NMR spectroscopy. The stability and in vitro release profile of nanoparticles were inspected, and anticancer efficacy was scrutinized in terms of in vitro cytotoxicity, oxidative stress and apoptosis biomarkers, and cell cycle arrest. In vivo tumor regression and host survival studies were executed in Ehrlich ascites carcinoma (EAC) cell-bearing Swiss albino mice. The drug uptake of highly stable PLGA-HSP-TF NPs was accomplished effectively in MDA-MB-231 cells and showed the pH-dependent intracellular release of HSP, which generated excessive intracellular reactive oxygen species (ROS) that led to oxidative assault to the TNBC cells. This elevated ROS dropped the mitochondrial membrane potential and triggered apoptosis-mediated cell death by arresting the cell cycle at the G0/G1 phase. Furthermore, PLGA-HSP-TF NPs unveiled significant in vivo Ehrlich ascites carcinoma regression and host survival compared to free HSP with minimum toxicity at a minimum dose of 20 mg/kg body weight. The study divulges that PLGA-HSP-TF NPs may be an astounding anticancer nanocandidate for aggressive triple-negative breast cancer therapy. |
