International audienceA new synthetic pathway for the direct synthesis of water soluble gold nanoparticles (GNPs) already possessing terminal alkene functional groups was developed. This is achieved by using synthesized (1-hydroxy-1-phosphonopent-4-enyl)phosphonic acid (HMBPene), presenting advantages of the well known bisphosphonate coating applied to colloidal gold instead of metal oxides. The proposed protocol allowed an accurate control of the particle size in the 13–20 nm diameter range with a high spherical uniformity, which is a crucial point for these colloids' properties. We have shown that it is possible to synthesize a functionalized nanoplatform in a one-pot one-phase process with a sacrificial molecule as reductant, pH mediator and capping agent

Gold nanoraspberries were synthesized by a seed-mediated synthesis with polyethylene glycol-functionalized bisphosphonates.

Gold nanoparticles can act as photothermal agents to generate local tumor heating and subsequent depletion upon laser exposure. Herein, photothermal heating of four gold nanoparticles and the resulting induced cancer cell death are systematically assessed, within extra‐ or intracellular localizations. Two state‐of‐the‐art gold nanorods are compared with small nanospheres (single‐core) and nanoraspberries (multicore). Heat generation is measured in water dispersion and in cancer cells, using lasers at wavelengths of 680, 808, and 1064 nm, covering the entire range used in photothermal therapy, defined as near infrared first (NIR‐I) and second (NIR‐II) windows, with NIR‐II offering more tissue penetration. When dispersed in water, gold nanospheres provide no significant heating, gold nanorods are efficient in NIR‐I, and only gold nanoraspberries are still heating in NIR‐II. However, in cells, due to endosomal confinement, all nanoparticles present an absorption red‐shift translating visible and NIR‐I absorbing nanoparticles into effective NIR‐I and NIR‐II nanoheaters, respectively. The gold nanorods then become competitive with the multicore nanoparticles (nanoraspberries) in NIR‐II. Similarly, once in cells, gold nanospheres can be envisaged for NIR‐I heating. Remarkably, nanoraspberries are efficient nanoheaters, whatever the laser applied, and the extra‐ versus intra‐cellular localization demonstrates treatment versatility.

Inverse electron demand Diels-Alder (iEDDA) was evaluated for the functionalization of gold nanoparticles. The reaction was first modelled with the free coating molecule 1-hydroxy-1,1-methylenebisphosphonate bearing an alkene functionality (HMBPene). A model tetrazine 3,6-dipyridin-2-yl-1,2,4,5-tetrazine (pyTz) was used, kinetic of the reaction was calculated and coupling products were analysed by NMR and HRMS. The reaction was then transposed at the nanoparticle surface. Gold nanoparticles bearing an alkene functionality were obtained using a one-pot methodology with HMBPene and the tetrazine click chemistry was evaluated at their surface using pyTz. The successful coupling was assessed by XPS measurements. This click-methodology was extended to the conjugation of a NIR probe at the NP surface.

Click synthesis of pegylated bisphosphonates for one pot preparation of stable gold nanoparticles.

A gold therapeutic nanoplatform with the same molecule used as reductant, coating and therapeutic agent has been developed in a one-pot, one-phase process using alendronate, a drug from the bisphosphonate family known for its antitumor effects. In addition, the core made of gold nanoparticles (NPs) brings thermal functionalities under irradiation within the first biological window (650–900 nm). The Au@alendronate nanoplatform thus provided a combined antitumor activity through drug delivery and photothermal therapy. Au@alendronate NPs inhibited in vitro the proliferation of prostate cancer cells (PC3) in a dose-dependent manner, with an IC50 value of 100 µM. Under NIR irradiation a temperature increase was observed leading to a reduction of the IC50 value to 1 µM, with total tumor cell death at 100 µM.

In article number 1900284, Yoann Lalatonne, Claire Wilhelm, and co‐workers assess the photothermal potential of gold nano‐spheres, rods, and raspberries‐like multi‐cores outside cancer cells (extracellular environment) or internalized within (intracellular), evidencing that the bio‐processing of gold nanomaterials can be highly beneficial for cancer therapy.