Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumour with limited treatment options and a poor prognosis. Therapeutic failure is driven by multiple barriers, including the blood–brain barrier (BBB), the tumour microenvironment (TME), and intratumoural heterogeneity. Conventional delivery systems often fail to achieve sufficient drug accumulation or controlled release within the tumour. In this review, we outline a theoretical framework for the design of ligand-functionalised magnetic lipid nanoparticles (MF-R-LNs), a multifunctional nanoplatform that integrates active targeting, stimuli-responsive drug release, and external magnetic-field control. The proposed MF-R-LNs incorporate superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic guidance and hyperthermia; polyethylene glycol (PEG) for extended circulation; and surface ligands such as peptides, antibodies, or aptamers to target GBM-specific receptors including epidermal growth factor receptor (EGFR), Interleukin-13 receptor alpha-2 (IL-13Rα2), and integrins. Triggered release mechanisms such as pH-sensitive lipids, redox cleavable linkers, and enzyme-responsive coatings enable selective drug release within the TME. Magnetic hyperthermia serves as both a therapeutic modality and a remote trigger to enhance release and tumour penetration. This modular design offers a theoretically robust strategy to overcome the key physiological and therapeutic barriers in GBM. We discuss the rationale behind each design feature, explore potential synergies, and highlight translational challenges such as tumour heterogeneity, manufacturing complexity, and safety concerns. Despite encouraging preclinical evidence, clinical translation faces substantial hurdles, notably patient-specific heterogeneity and scalable GMP manufacturing/characterisation of multi-component nanoplatforms. While preclinical validation remains necessary, this framework may inform future efforts to develop spatiotemporally controlled, multifunctional therapeutics for glioblastoma. This manuscript is a conceptual framework review that synthesises current strategies into actionable guidance for designing and reporting MF-R-LNs for GBM.
多形性胶质母细胞瘤（GBM）是一种高度侵袭性的原发性脑肿瘤，治疗手段有限且预后不良。治疗失败源于多重屏障，包括血脑屏障（BBB）、肿瘤微环境（TME）以及肿瘤内异质性。传统递送系统常难以在肿瘤内实现足够的药物蓄积或可控释放。本综述提出了一种配体功能化磁性脂质纳米粒（MF-R-LNs）设计的理论框架，该多功能纳米平台整合了主动靶向、刺激响应药物释放和外磁场控制。所设计的MF-R-LNs包含用于磁引导和热疗的超顺磁性氧化铁纳米粒（SPIONs）、延长循环时间的聚乙二醇（PEG），以及靶向GBM特异性受体（如表皮生长因子受体（EGFR）、白细胞介素-13受体α2（IL-13Rα2）和整合素）的肽段、抗体或适配体等表面配体。pH敏感脂质、氧化还原可裂解连接子和酶响应涂层等触发释放机制可实现TME内的选择性药物释放。磁热疗既可作为一种治疗方式，也可作为增强药物释放和肿瘤渗透的远程触发手段。这种模块化设计为克服GBM的关键生理和治疗屏障提供了理论上的稳健策略。我们讨论了各设计特征的理论依据，探讨了潜在的协同效应，并强调了转化挑战，如肿瘤异质性、制造复杂性和安全性问题。尽管临床前证据令人鼓舞，但临床转化仍面临重大障碍，特别是患者特异性异质性和多组分纳米平台的可扩展GMP生产/表征。虽然仍需进行临床前验证，但该框架可为未来开发时空可控的多功能胶质母细胞瘤治疗策略提供参考。本文作为概念框架综述，将现有策略整合为可操作的指导原则，用于设计和报告针对GBM的MF-R-LNs。
肿瘤(癌症)患者之家