ARTICLE IN PRESS JID: ACTBIO [m5G;September 11, 2020;16:38] Acta Biomaterialia xxx (xxxx) xxx Contents lists available at ScienceDirect Acta Biomaterialia journal homepage: www.elsevier.com/locate/actbio Review article Strategies to improve the photothermal capacity of gold-based nanomedicines Ariana S.C. Gonçalves a , Carolina F. Rodrigues a , André F. Moreira a,∗ , Ilídio J. Correia a,b,∗ a CICS-UBI – Health Sciences Research Centre, Universidade da Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal b CIEPQF — Departamento de Engenharia Química, Universidade de Coimbra, Rua Sílvio Lima, 3030-790 Coimbra, Portugal a r t i c l e i n f o Article history: Received 17 July 2020 Revised 27 August 2020 Accepted 2 September 2020 Available online xxx Keywords: Gold nanoparticles Photothermal therapy Cancer NIR radiation a b s t r a c t The plasmonic photothermal properties of gold nanoparticles have been widely explored in the biomed- ical field to mediate a photothermal effect in response to the irradiation with an external light source. Particularly, in cancer therapy, the physicochemical properties of gold-based nanomaterials allow them to efficiently accumulate in the tumor tissue and then mediate the light-triggered thermal destruction of cancer cells with high spatial-temporal control. Nevertheless, the gold nanomaterials can be produced with different shapes, sizes, and organizations such as nanospheres, nanorods, nanocages, nanoshells, and nanoclusters. These gold nanostructures will present different plasmonic photothermal properties that can impact cancer thermal ablation. This review analyses the application of gold-based nanomaterials in cancer photothermal therapy, emphasizing the main parameters that affect its light-to-heat conversion ef- ficiency and consequently the photothermal potential. The different shapes/organizations (clusters, shells, rods, stars, cages) of gold nanomaterials and the parameters that can be fine-tuned to improve the pho- tothermal capacity are presented. Moreover, the gold nanostructures combination with other materials (e.g. silica, graphene, and iron oxide) or small molecules (e.g. indocyanine green and IR780) to improve the nanomaterials photothermal capacity is also overviewed. © 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. 1. Introduction Nanoparticle-mediated photothermal therapy (PTT) has been widely explored as a standalone or combinatorial therapy for can- cer because it enables to focus of the hyperthermia in the tumor avoiding damages to the healthy tissues [1]. This therapy takes ad- vantage of the nanomaterials’ physicochemical properties, which confer to them tumor selectivity [2]. At the tumor site, the nano- materials will be irradiated with a light source promoting the gen- eration of heat [3]. This tumor localized increments of tempera- ture can sensitize the cells to other therapeutic applications (e.g. chemotherapy) or even induce several cellular damages that can ultimately lead to apoptosis or necrosis when reaching tempera- tures superior to 40°C [4,5]. In this approach, the application of NIR radiation (700-1200 nm) to activate the nanomaterials is cru- cial since the major components of the human body (e.g. water, proteins, collagen, hemoglobin) present an insignificant absorption in this region of the electromagnetic spectrum [6]. Moreover, this optical transparency minimizes the absorption and scattering phe- ∗ Corresponding authors. E-mail addresses: afmoreira@fcsaude.ubi.pt (A.F. Moreira), icorreia@ubi.pt (I.J. Correia). nomena, which improve radiation penetration and photothermal efficacy [7]. Several types of nanomaterials can be applied as photother- mal agents, such as carbon nanotubes [8], graphene oxide [9], polyaniline [10], and gold [11], or even conjugated with small molecules (e.g. IR780 [12], indocyanine green (ICG) [13]) to me- diate PTT. Among them, gold-based nanoparticles possess unique physicochemical properties making them one of the most explored nanoplatforms in PTT [14]. Gold is known as one of the least re- active metals, presents a high variability in terms of shape, size and surface chemistry, and high resistance to degradation and ox- idation [15]. Moreover, the localized surface plasmon resonance (LSPR) phenomenon observed in gold nanoparticles can be fine- tuned by optimizing the size and shape to render them a strong absorption in the NIR region increasing their efficiency as PTT agents [16–18]. Additionally, the gold nanomaterials can also act as contrast agents in computerized tomography (CT) and magnetic resonance imaging (MRI), mass attenuation of gold is superior to that of the iodinated contrast agents commonly used in the clinic, or even prompt the photoacoustic imaging (PAI) [19–21]. Other- wise, the gold nanoparticles affinity to interact with compounds containing thiol or disulfide groups can be explored for modify- ing the surface of the nanoparticles with passivating agents that https://doi.org/10.1016/j.actbio.2020.09.008 1742-7061/© 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. Please cite this article as: A.S.C. Gonçalves, C.F. Rodrigues and A.F. Moreira et al., Strategies to improve the photothermal capacity of gold-based nanomedicines, Acta Biomaterialia, https://doi.org/10.1016/j.actbio.2020.09.008