Department of Pharmaceutical Technology and Food Engineering, Complutense University, 28040 Madrid, Spain.
Department of Pharmaceutical Technology and Food Engineering, Complutense University, 28040 Madrid, Spain; University Institute of Industrial Pharmacy, Complutense University, Madrid, Spain.
Acta Biomater. 2018 Jun;73:52-63. doi: 10.1016/j.actbio.2018.04.029. Epub 2018 Apr 17.
Malignant brain tumors still represent an unmet medical need given their rapid progression and often fatal outcome within months of diagnosis. Given their extremely heterogeneous nature, the assumption that a single therapy could be beneficial for all patients is no longer plausible. Hence, early feedback on drug accumulation at the tumor site and on tumor response to treatment would help tailor therapies to each patient's individual needs for personalized medicine. In this context, at the intersection between imaging and therapy, theranostic nanomedicine is a promising new technique for individualized management of malignant brain tumors. Although brain nanotheranostics has yet to be translated into clinical practice, this field is now a research hotspot due to the growing demand for personalized therapies. In this review, the barriers to the clinical implementation of theranostic nanomedicine for tracking tumor responses to treatment and for guiding stimulus-activated therapies and surgical resection of malignant brain tumors are discussed. Likewise, the criteria that nanotheranostic systems need to fulfil to become clinically relevant formulations are analyzed in depth, focusing on theranostic agents already tested in vivo. Currently, magnetic nanoparticles exploiting brain targeting strategies represent the first generation of preclinical theranostic nanomedicines for the management of malignant brain tumors.
The development of nanocarriers that can be used both in imaging studies and the treatment of brain tumors could help identify which patients are most and least likely to respond to a given treatment. This will enable clinicians to adapt the therapy to the needs of the patient and avoid overdosing non-responders. Given the many different approaches to non-invasive techniques for imaging and treating brain tumors, it is important to focus on the strategies most likely to be implemented and to design the most feasible theranostic biomaterials that will bring nanotheranostics one step closer to clinical practice.
鉴于恶性脑肿瘤的快速进展以及在诊断后数月内常导致致命后果,其仍然是未满足的医疗需求。鉴于其具有极其异质性的性质,认为单一疗法可能对所有患者都有益的假设已不再合理。因此,尽早获得药物在肿瘤部位的积累情况以及肿瘤对治疗的反应的反馈信息,将有助于根据每位患者的个体需求来定制治疗方案,实现个性化医疗。在这种情况下,影像与治疗相结合,治疗性纳米医学是一种很有前途的新方法,可用于恶性脑肿瘤的个体化管理。尽管脑纳米治疗学尚未转化为临床实践,但由于对个性化治疗的需求不断增长,该领域现在已成为研究热点。在本文中,我们讨论了用于跟踪肿瘤对治疗的反应并指导刺激激活治疗和恶性脑肿瘤手术切除的治疗性纳米医学的临床实施所面临的障碍。同样,我们深入分析了纳米治疗系统需要满足的条件,以使其成为具有临床相关性的制剂,重点关注已经在体内进行测试的治疗剂。目前,利用脑靶向策略的磁性纳米颗粒代表了第一代用于管理恶性脑肿瘤的临床前治疗性纳米医学。
开发既能用于成像研究又能用于治疗脑肿瘤的纳米载体,有助于确定哪些患者最有可能以及最不可能对特定治疗方法产生反应。这将使临床医生能够根据患者的需求调整治疗方法,并避免对无反应者过度治疗。鉴于用于脑肿瘤成像和治疗的非侵入性技术有很多不同的方法,因此重要的是要关注最有可能实施的策略,并设计最可行的治疗性生物材料,以使纳米治疗学更接近临床实践。