Magnetic Nanoparticle-Induced Hyperthermia with Appropriate Payloads: Paul Ehrlich’s “Magic (Nano)bullet” for Cancer Theranostics?

Nilroy R. Datta, Sunil Krishnan, Daniel E. Speiser, Esra Neufeld, Niels Kuster, Stefan Bodis, and Heinrich Hofmann, Cancer Treatment Reviews, Volume 50, pp. 217–227, online September 2016

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 with 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 be extravasated passively into the tumour tissues preferentially over adjacent normal tissues due to their enhanced permeability and retention effects. 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 empowering multifunctional tumour-specific payloads based on radiotheranostics (for both imaging and radiotherapy), chemotherapeutic drug delivery, immunotherapy, and gene-silencing therapy. Such a (nano)bullet could realise the “magic bullet” conceived by Paul Ehrich more than a century ago. This review 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.

The scientific and technical impact of the review paper can be summarized as:

• Magnetic nanoparticles with appropriate payloads can be effective cancer theranostic agents
• Critical payloads can be designed to offer personalized cancer diagnosis and therapy
• Magnetic nanoparticles enable integration of thermochemoradio-, immuno-, and gene-silencing-therapies
• Magnetic nanoparticle hyperthermis treatment planning for thermal dosimetry and optimization of treatment personalization is feasible
• Image-based, multiphysics-multiscale simulation, and physiology modelling are key for such treatment planning

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