Ramayanam Navakanth Raju, Bukke Sarad Pawar Naik, Moka Murali Krishna, Dehingia Himanshu, Bordoloi Aditya, Debbarma Riya, Kudumula Purushothama Reddy, Vuyyala Balakrishna, Prasad P Dharani, Catherine Akugizibwe
Department of Pharmacy Practice, Faculty of Pharmacy, Dr. M.G.R Educational and Research Institution, Chennai, Tamil Nadu, 600077, India.
Department of Pharmaceutics and Pharmaceutical Technology, Kampala International University, Western Campus, P.O. Box 71, Ishaka, Bushenyi, Uganda.
Discov Nano. 2025 Jul 14;20(1):111. doi: 10.1186/s11671-025-04308-5.
Triple-negative breast cancer (TNBC) is a prevalent and aggressive subtype of breast cancer, accounting for approximately 10-15% of all cases. Its lack of hormone receptors and poor clinical prognosis make targeted therapy particularly challenging, leaving chemotherapy as the mainstay treatment. However, conventional chemotherapy is associated with significant limitations, including cardiotoxicity and inadequate tumor cell specificity. Nanoparticle-based drug delivery systems have emerged as a promising strategy for enhancing the therapeutic efficacy of doxorubicin (DOX) in TNBC. Among these, cell membrane-coated nanoparticles, exosome-sheathed porous silica nanoparticles, and FZD7-targeted nanoparticles have demonstrated substantial potential. These platforms improve drug delivery efficiency while minimizing systemic toxicity and adverse effects. Cell membrane-coated nanoparticles evade immune surveillance, allowing for selective targeting of TNBC cells. Exosome-sheathed nanoparticles facilitate the co-delivery of DOX with other therapeutic agents aimed at inhibiting cancer stem cell-driven epithelial-to-mesenchymal transition. FZD7-targeted nanoparticles enhance DOX accumulation within tumor cells by binding specifically to FZD7 receptors, leading to increased apoptosis and reduced cancer cell metabolic activity. This review aims to examine recent advancements in nanoparticle-based delivery systems for DOX in the treatment of TNBC. It further explores various formulations-including liposomes and polymeric nanoparticles-used for DOX delivery, assesses active and passive targeting strategies, and evaluates the advantages of controlled drug release. The review also identifies current gaps in the literature and proposes future research directions to advance the clinical applicability of these systems. Emerging concepts such as the active transport and retention mechanism and macrophage-mediated delivery systems offer new opportunities to improve tumor localization and retention of DOX-loaded nanoparticles. Collectively, these developments underscore the transformative potential of nanoparticle-based DOX delivery in revolutionizing TNBC therapy.
三阴性乳腺癌(TNBC)是一种常见且侵袭性强的乳腺癌亚型,约占所有病例的10 - 15%。其缺乏激素受体且临床预后较差,使得靶向治疗极具挑战性,化疗仍是主要治疗手段。然而,传统化疗存在显著局限性,包括心脏毒性和肿瘤细胞特异性不足。基于纳米颗粒的药物递送系统已成为提高阿霉素(DOX)治疗TNBC疗效的一种有前景的策略。其中,细胞膜包覆纳米颗粒、外泌体包裹的多孔二氧化硅纳米颗粒和靶向FZD7的纳米颗粒已展现出巨大潜力。这些平台提高了药物递送效率,同时将全身毒性和不良反应降至最低。细胞膜包覆纳米颗粒可逃避免疫监视,实现对TNBC细胞的选择性靶向。外泌体包裹的纳米颗粒有助于将DOX与其他旨在抑制癌症干细胞驱动的上皮-间质转化的治疗剂共同递送。靶向FZD7的纳米颗粒通过与FZD7受体特异性结合,增强DOX在肿瘤细胞内的积累,导致细胞凋亡增加和癌细胞代谢活性降低。本综述旨在探讨基于纳米颗粒的DOX递送系统在TNBC治疗中的最新进展。它进一步探索了用于DOX递送的各种制剂,包括脂质体和聚合物纳米颗粒,评估了主动和被动靶向策略,并评估了控释药物的优势。该综述还指出了当前文献中的空白,并提出了未来的研究方向,以推进这些系统的临床应用。主动转运和滞留机制以及巨噬细胞介导的递送系统等新兴概念为改善载DOX纳米颗粒的肿瘤定位和滞留提供了新机会。总体而言,这些进展突显了基于纳米颗粒的DOX递送在彻底改变TNBC治疗方面的变革潜力。
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