Verma Yashasvi, Khan Insha, Dongsar Tenzin Tsering, Alsayari Abdulrhman, Wahab Shadma, Sahebkar Amirhossein, Kesharwani Prashant
Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
Department of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia.
Int J Biol Macromol. 2025 Jul;318(Pt 2):145125. doi: 10.1016/j.ijbiomac.2025.145125. Epub 2025 Jun 9.
Breast cancer remains a leading cause of cancer-related mortality in women, accounting for 23.8 % of all female cancer cases. Existing therapies often lack tumor specificity, leading to severe off-target toxicity, dose-limiting side effects, and poor patient compliance. These limitations underscore the urgent need for innovative strategies that enhance therapeutic precision. AS1411 aptamer-based nanomaterials have emerged as a transformative solution, leveraging the aptamer's high-affinity binding to nucleolin, a receptor overexpressed on breast cancer cells, to enable targeted drug delivery, imaging, and combinatorial therapies. This review explores the potential applications of AS1411-based nanoformulations and discussed various nanoformulations for the same in the treatment of breast cancer. Notably, categorizing advancements into platforms including DNA nanocarriers (e.g., MUC1-Td-AS1411 nanoscaffold), which enhance drug retention and therapeutic outcomes; polymeric nanoparticles (e.g., AS1411-functionalized AuNBP-Gd₂O₃/dBSA), which provide controlled release and improved cellular uptake; and metallic nanoparticles (e.g., AS1411-functionalized AuNBP-Gd₂O₃/dBSA), which enable dual-modal imaging and effective tumor ablation. These advancements highlight the multifunctional potential of AS1411-based nanoformulations in advancing breast cancer treatment, which combine precise targeting with reduced systemic toxicity, and compatibility. However, challenges such as large-scale synthesis complexity, immunogenicity of DNA-based carriers, and regulatory barriers must be addressed to facilitate clinical translation. Collaborative efforts to optimize scalable manufacturing and conduct comprehensive immunotoxicity studies will be pivotal in advancing these nanotherapeutics from preclinical promise to clinical reality, ultimately offering a safer, more effective paradigm for breast cancer treatment.
乳腺癌仍然是女性癌症相关死亡的主要原因,占所有女性癌症病例的23.8%。现有疗法往往缺乏肿瘤特异性,导致严重的脱靶毒性、剂量限制性副作用和患者依从性差。这些局限性凸显了对提高治疗精准度的创新策略的迫切需求。基于AS1411适配体的纳米材料已成为一种变革性解决方案,利用适配体与核仁素的高亲和力结合,核仁素是一种在乳腺癌细胞上过度表达的受体,以实现靶向药物递送、成像和联合治疗。本文综述探讨了基于AS1411的纳米制剂的潜在应用,并讨论了其在乳腺癌治疗中的各种纳米制剂。值得注意的是,将进展分类为不同平台,包括DNA纳米载体(如MUC1-Td-AS1411纳米支架),可提高药物保留率和治疗效果;聚合物纳米颗粒(如AS1411功能化的AuNBP-Gd₂O₃/dBSA),可提供控释并改善细胞摄取;以及金属纳米颗粒(如AS1411功能化的AuNBP-Gd₂O₃/dBSA),可实现双模态成像和有效的肿瘤消融。这些进展突出了基于AS1411的纳米制剂在推进乳腺癌治疗方面的多功能潜力,其将精确靶向与降低的全身毒性和兼容性相结合。然而,必须解决大规模合成复杂性、基于DNA的载体的免疫原性和监管障碍等挑战,以促进临床转化。优化可扩展制造并进行全面免疫毒性研究的合作努力对于将这些纳米疗法从临床前的前景推进到临床现实至关重要,最终为乳腺癌治疗提供更安全、更有效的范例。