Centre for Radiation Oncology, KSA-KSB, Kantonsspital Aarau, Aarau, Switzerland.
Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Cancer Treat Rev. 2016 Nov;50:217-227. doi: 10.1016/j.ctrv.2016.09.016. Epub 2016 Oct 3.
Effective multimodal cancer management requires the optimal integration of diagnostic and therapeutic modalities. Radiation therapy, chemotherapy and immunotherapy, alone or in combination, are integral parts of various cancer treatment protocols. Hyperthermia at 39-45°C is a potent radiosensitiser and has been shown to improve therapeutic outcomes in various tumours through its synergy with chemotherapy. Gene silencing approaches, using small interfering RNAs and microRNAs, are also being explored in clinical trials in oncology. The rapid developments in multifunctional nanoparticles provide ample opportunities to integrate both diagnostic and therapeutic modalities into a single effective cancer "theranostic" vector. Nanoparticles could extravasate passively into the tumour tissues in preference to the adjacent normal tissues by capitalizing on the enhanced permeability and retention effect. Tumour targeting might be further augmented by conjugating tumour-specific peptides and antibodies onto the surface of these nanoparticles or by activation through electromagnetic radiations, laser or ultrasound. Magnetic nanoparticles can induce hyperthermia in the presence of an alternating magnetic field, thereby multifunctionally with tumour-specific payloads empowering tumour specific radiotheranostics (for both imaging and radiotherapy), chemotherapy drug delivery, immunotherapy and gene silencing therapy. Such a (nano)bullet could realise the "magic bullet" conceived by Paul Ehrlich more than a century ago. This article discusses the various aspects of this "magic (nano)bullet" and the challenges that need to be addressed to usher in this new paradigm in modern cancer diagnostics and therapeutics.
有效的多模式癌症管理需要最佳整合诊断和治疗模式。单独或联合使用放射治疗、化学疗法和免疫疗法是各种癌症治疗方案的组成部分。39-45°C 的高热是一种有效的放射增敏剂,通过与化学疗法的协同作用,已显示可改善各种肿瘤的治疗效果。使用小干扰 RNA 和 microRNA 的基因沉默方法也正在肿瘤学临床试验中进行探索。多功能纳米粒子的快速发展为将诊断和治疗模式整合到单个有效的癌症“治疗诊断”载体中提供了充足的机会。纳米粒子可以通过利用增强的通透性和保留效应,被动地渗出到肿瘤组织中,而不是相邻的正常组织中。通过将肿瘤特异性肽和抗体连接到这些纳米粒子的表面,或通过电磁辐射、激光或超声激活,肿瘤靶向性可以进一步增强。磁性纳米粒子可以在交变磁场的存在下诱导热疗,从而与肿瘤特异性有效载荷多功能化,实现肿瘤特异性放射治疗诊断(用于成像和放射治疗)、化疗药物递送、免疫治疗和基因沉默治疗。这样的(纳米)子弹可以实现一个多世纪前保罗·埃尔利希构思的“魔弹”。本文讨论了这种“魔弹”的各个方面以及需要解决的挑战,以开启现代癌症诊断和治疗的这一新范例。
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