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Multifunctional Highly Compliant Implants for Cancer

Kruv, A.; Canon Bermudez, G. S.; Voitsekhivska, T.; Lebanov, A.; Fassbender, J.; Yevsa, T.; Makarov, D.

Cancer is one of the main death reasons worldwide [1]. Radio- and chemotherapies, which are the most common approaches to combat this disease, cause severe side effects due to their non-selective nature [2]. As an alternative paradigm, a targeted cancer therapy has recently emerged. This method aims to affect only cancer cells thus spare the healthy tissues [3].
The large fraction of the targeted therapies relay on drug delivery in nanovectors (e.g. micelles, dendrimers) to the tumour site via vascular system followed by the drug release in response to binding to a certain molecule, local environment (e.g. pH) or externally provided heat [4]. These methods suffer from delivery complexity (e.g. due to multiple physiological barriers), non-reliability of the release mechanism, difficulty in organising the feedback for precise control over the process as well as toxicity and stability concerns [4,5].
In order to overcome these limitations, we propose an alternative approach to the targeted cancer treatment (liver cancer is used as a case study) which relies on the implantation at the tumour site of an ultra-thin flexible device comprising a resistive heater and temperature sensor. The devices are prepared on a 6 micrometer thick PET foil. This foil thickness was found to be optimal as it provides the best compliancy to the very soft liver tissue and does not mechanically damage the tissue. The heater can heat the tissue to a pre-defined temperature of up to 55 °C even when the driving current is in the range of 10 mA. The integrated temperature sensor provides a real-time feedback about the on-site thermal impact. We demonstrate a proof-of-the-concept prototype together with the evaluation of its electrical and mechanical performance and the results of the first clinical trials on mice models.
This device allows realizing several negative for tumour interactions including thermal impact all the way up to burning the tissue, highly localized drug release, enhancement of immune response and drug uptake [6]. In addition, it raises the possibility to establish precise control over temperature and potentially evaluate the treatment effects which are of fundamental importance for the development of the new models for cancer research especially in the case of such a severe one as liver cancer.

[1] A. Jemal et al., CA: a cancer journal for clinicians, 61(2), 69-90 (2011).
[2] Padma, V. V. (2015). An overview of targeted cancer therapy. BioMedicine, 5(4), 19-19.
[3] A. A. Alexander-Bryant et al., Advances in cancer research, 118, 1 (2012).
[4] J. Shi et al., Nature Reviews Cancer, 17, 20 (2017).
[5] M. Ferrari, Nature Reviews Cancer 5, 161 (2005).
[6] K. F. Chu et al., Nature Reviews Cancer 14, 199 (2014).

Keywords: cancer threatment; ultra-thin flexible heater

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Publ.-Id: 26758