Patil Chethan, Priyanka R, Harshitha B M, Oshik S, Yashwanth S, Darshan B R, Patil Shradha, Prajwal K A, Naik Prasiddhi, Goudanavar Prakash, Mallamma T
Department of Pharmaceutics, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, B.G. Nagara, Mandya, 571418, Karnataka, India.
Med Oncol. 2025 Aug 7;42(9):413. doi: 10.1007/s12032-025-02944-6.
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. It is hard to treat because it is very invasive, has a lot of genetic variation, and the blood-brain barrier (BBB) limits its growth. Traditional GBM treatments, including surgery, radiation and chemotherapy have only marginally improved survival requiring a paradigm shift. This review starts a new way of thinking about how to treat GBM by combining multi-responsive nanotheranostics, next-generation genome engineering, and AI-enabled stratification. The study compares smart nanocarriers that can transport payloads accurately and only when needed. CRISPR/Cas systems are useful for directly editing oncogenes, controlling GBM signaling cascades, making resistant cells sensitive again, and changing the ways that cells avoid the immune system. Nanoparticle-mediated CRISPR delivery and BBB disruption approaches, including targeted ultrasound, receptor-mediated transcytosis, and exosome-based delivery, could help get around the neuroprotective shield without damaging it. This review investigates the molecular aspects of the BBB, highlighting its dual role as a metabolic and efflux transporter-mediated barrier, and assesses cutting-edge nanocarrier systems, in particular hybrid exosome-nanoparticle designs, that aim to circumvent these limitations. Additionally, it explores the current limitations and possible future applications of gene editing tools and AI models for navigating the genomic instability and ever-changing tumor microenvironment of GBM. This study also discusses the ethical and legal issues related to these developing technologies, therefore stressing the need for clinically feasible, ethically controlled innovation pipelines. With an emphasis on cutting-edge research, this review delves into emerging areas such as nanotheranostics, cellular composition of GBM, CRISPR-based gene editing, AI-enabled precision medicine, and targeted disruption of the blood-brain barrier.
胶质母细胞瘤（GBM）是成人中最具侵袭性的原发性脑肿瘤。由于其具有很强的侵袭性、大量的基因变异以及血脑屏障（BBB）限制其生长，因此难以治疗。包括手术、放疗和化疗在内的传统GBM治疗方法仅略微提高了生存率，需要一种范式转变。本综述开启了一种新的思维方式，即通过结合多响应纳米诊疗技术、下一代基因组工程和人工智能分层来治疗GBM。该研究比较了能够在需要时准确运输有效载荷的智能纳米载体。CRISPR/Cas系统可用于直接编辑癌基因、控制GBM信号级联反应、使耐药细胞再次敏感以及改变细胞逃避免疫系统的方式。纳米颗粒介导的CRISPR递送和血脑屏障破坏方法，包括靶向超声、受体介导的转胞吞作用和基于外泌体的递送，有助于绕过神经保护屏障而不破坏它。本综述研究了血脑屏障的分子方面，强调了其作为代谢和外排转运体介导的屏障的双重作用，并评估了旨在克服这些限制的前沿纳米载体系统，特别是外泌体-纳米颗粒混合设计。此外，它还探讨了基因编辑工具和人工智能模型在应对GBM的基因组不稳定性和不断变化的肿瘤微环境方面的当前局限性和可能的未来应用。本研究还讨论了与这些新兴技术相关的伦理和法律问题，因此强调了临床可行、符合伦理规范的创新管道的必要性。本综述着重于前沿研究，深入探讨了纳米诊疗技术、GBM的细胞组成、基于CRISPR的基因编辑、人工智能精准医学以及血脑屏障的靶向破坏等新兴领域。
