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Gold nanorods (AuNRs) can combine therapeutic hyperthermia with diagnostic features, representing a smart choice to address personalized cancer treatments. In this regard, a crucial quest is the selection of the right biocompatible coating agent able to stabilize them in the physiological environment, further endowing the possibility to load bioactive molecules and/or targeting moieties. Therefore, AuNRs optical properties can be successfully merged with advantageous materials features to obtain selective photothermal therapy (PTT) systems. Here, the natural materials lipoic acid (LA) and the polysaccharide gellan gum (GG) were chosen to prepare three types of stabilized gold nanorods, using LA (AuNRs/LA), a layered coating of LA and GG (AuNRs/LA,GG) or a newly synthesized covalent derivative of LA and GG (AuNRs/GG-LA). The samples displayed diverse stability and dispersibility. Hydrodynamic diameters and surface potential analyses confirmed the nanometric size (100–200 nm) and showed surface charges ranging from +19.5 to −25.6 mV. Particular attention was thus paid to analyze the differences between hyperthermia properties exhibited after near-infrared (NIR) laser irradiation. Furthermore, the cytocompatibility and photothermal effect were tested on HCT116 human colon cancer cell line. Collected data have finally allowed selecting AuNRs/LA,GG as the best candidate for possible use in PTT of cancer. [ABSTRACT FROM AUTHOR]

[Display omitted] • Combined photothermal/photodynamic therapy could improve cancer treatment efficacy. • Natural coatings allow gold nanorods (AuNRs) in vivo administration. • Verteporfin is an intriguing agent for the photodynamic therapy of colon cancer. • Drug-free AuNRs decelerate colon cancer growth via photothermal therapy. • Verteporfin-AuNRs eradicate colon cancer through photothermal/photodynamic therapy. The high incidence of cancer recurrences and the frequent occurrence of multidrug resistance often stem from a poorly selective and inefficient antineoplastic therapy, responsible for the onset of undesired side effects as well. A combination of minimal-invasive approaches could thus be a useful strategy to surmount these shortcomings, achieving a safe and solid cancer therapy. Herein, a multi-therapeutic nanotool was designed by merging the photothermal properties of gold nanorods (AuNRs) with the photodynamic activity of the photosensitizer verteporfin. AuNRs were coated with the natural materials lipoic acid and gellan gum (AuNRs_LA,GG) and subsequently loaded with verteporfin (AuNRs_LA,GG/Vert) producing stable colloidal dispersions. AuNRs_LA,GG/Vert were characterized in terms of stability, size and morphology. The hyperthermia exhibited after NIR excitation (810 nm) was also evaluated to highlight the effect on increasing the drug released profile in intra-tumoral mimicking media, as well as cytotoxicity on human colon cancer cell line (HCT116). In vivo studies on HCT116 murine xenograft models were carried out to prove the ability of AuNRs_LA,GG to arrest the tumor growth via NIR laser-triggered hyperthermia. Furthermore, the complete xenograft depletion was demonstrated upon AuNRs_LA,GG/Vert administration by combined photothermal (PTT) and photodynamic (PDT) effects. [ABSTRACT FROM AUTHOR]