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.
ACS Appl Bio Mater. 2024 Nov 18;7(11):7556-7573. doi: 10.1021/acsabm.4c01131. Epub 2024 Nov 6.
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--glycolic acid) (PLGA) nanobioconjugate (PLGA-HSP-TF NPs) and the exploration of its and antineoplastic potential. PLGA nanoparticles (NPs), PLGA-HSP NPs, and PLGA-HSP-TF NPs were synthesized and characterized by DLS, FTIR, FE-SEM, and H NMR spectroscopy. The stability and release profile of nanoparticles were inspected, and anticancer efficacy was scrutinized in terms of cytotoxicity, oxidative stress and apoptosis biomarkers, and cell cycle arrest. 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 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.
三阴性乳腺癌（TNBC）因其快速恶化的生长、广泛的转移能力以及对标准当前治疗方法的耐药性，被认为是一种主要的侵袭性乳腺癌亚型。橙皮苷（HSP）是一种来自柑橘类水果的天然类黄酮，具有显著的抗癌功效，但由于其疏水性限制了其临床开发。本研究报告了一种生物相容性和 pH 响应的转铁蛋白（TF）受体靶向 HSP 负载的聚乳酸-乙醇酸（PLGA）纳米生物缀合物（PLGA-HSP-TF NPs）的制备，并探讨了其抗肿瘤潜能。通过 DLS、FTIR、FE-SEM 和 H NMR 光谱对 PLGA 纳米粒子（NPs）、PLGA-HSP NPs 和 PLGA-HSP-TF NPs 进行了合成和表征。考察了纳米粒子的稳定性和释放特性，并从细胞毒性、氧化应激和凋亡生物标志物以及细胞周期阻滞等方面考察了其抗肿瘤活性。在荷 Ehrlich 腹水癌（EAC）细胞的瑞士白化小鼠中进行了肿瘤消退和宿主存活研究。在 MDA-MB-231 细胞中有效实现了高度稳定的 PLGA-HSP-TF NPs 的药物摄取，并显示出 HSP 的 pH 依赖性细胞内释放，这导致了大量的细胞内活性氧（ROS）产生，从而对 TNBC 细胞造成氧化损伤。这种升高的 ROS 降低了线粒体膜电位，并通过将细胞周期阻滞在 G0/G1 期触发凋亡介导的细胞死亡。此外，与游离 HSP 相比，PLGA-HSP-TF NPs 显示出显著的 Ehrlich 腹水癌消退和宿主存活，并且在最低 20mg/kg 体重的最小剂量下具有最小的毒性。该研究表明，PLGA-HSP-TF NPs 可能是一种用于侵袭性三阴性乳腺癌治疗的令人惊讶的抗癌纳米候选药物。
