Koch Cancer Research Building, 1550 Orleans Street, Baltimore, MD, 21231, USA.
Koch Cancer Research Building, 1550 Orleans Street, Baltimore, MD, 21231, USA.
J Control Release. 2016 Oct 28;240:443-453. doi: 10.1016/j.jconrel.2016.03.031. Epub 2016 Mar 23.
Despite recent technological advancements and promising preclinical experiments, brain tumor patients are still met with limited treatment options. Some of the barriers to clinical improvements include the systemic toxicity of cytotoxic compounds, the impedance of the blood brain barrier (BBB), and the lack of therapeutic agents that can selectively target the intracranial tumor environment. To overcome such barriers, a number of chemotherapeutic agents and nucleic acid-based therapies are rapidly being synthesized and tested as new brain tumor-targeted delivery strategies. Novel carriers include liposomal and polymeric nanoparticles, wafers, microchips, microparticle-based nanoplatforms and cells-based vectors. Strong preclinical results suggest that these nanotechnologies are set to transform the therapeutic paradigm for brain tumor treatment. In addition to new tumoricidal agents, parallel work is also being conducted on the BBB front. Preclinical testing of chemical and physical modulation strategies is yielding improved intracranial concentrations. New diagnostic and therapeutic imaging techniques, such as high-intensity focused ultrasound and MRI-guided focused ultrasound, are being used to modulate the BBB in a more precise and non-invasive manner. This review details some of the tremendous advances that are being explored in current brain tumor targeted therapies, including local implant development, nanobiotechnology-based delivery strategies, and techniques of BBB manipulation.
尽管最近取得了技术进步和有前景的临床前实验，但脑瘤患者的治疗选择仍然有限。临床进展的一些障碍包括细胞毒性化合物的全身毒性、血脑屏障（BBB）的阻抗，以及缺乏能够选择性靶向颅内肿瘤环境的治疗剂。为了克服这些障碍，许多化疗药物和基于核酸的疗法正在被迅速合成和测试，作为新的脑瘤靶向递药策略。新型载体包括脂质体和聚合物纳米颗粒、载药晶片、微芯片、基于微粒的纳米平台和基于细胞的载体。强有力的临床前结果表明，这些纳米技术将改变脑瘤治疗的治疗模式。除了新的杀肿瘤剂，人们还在 BBB 方面开展平行工作。化学和物理调制策略的临床前测试正在产生改善的颅内浓度。新的诊断和治疗成像技术，如高强度聚焦超声和 MRI 引导的聚焦超声，正被用于以更精确和非侵入性的方式调节 BBB。这篇综述详细介绍了当前脑瘤靶向治疗中正在探索的一些巨大进展，包括局部植入物的发展、基于纳米生物技术的递药策略和 BBB 操作技术。
