TNP-HGNS

Self-Assembled Thermo-NanoProbes on Hollow Gold Nanoparticles For Theragnostic Applications

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 Obiettivo del progetto (Objective)

'The functionally controllable molecules that are activated upon irradiation, have received a significant attention as nano-scale delivery tools in biomedical applications. Among these, photolabile caged therapeutic molecules are chemically blocked species which can be liberated in their active form by exposure to ultraviolet (UV) radiation. By precise tuning of UV source, the use of these photosensitive probes becomes a unique tool to treat a selected biological target spatially and temporally. This technique has been successfully employed in a variety of biological studies; however, it is mostly limited to in vitro applications. The restriction is mainly due to the destructive effects of UV light which has shallow tissue penetration with strong absorption. Quite the contrary, near-infrared (NIR) radiation is known to have deep tissue penetration with minimum absorption. This outstanding property of NIR, with the aid of strong NIR absorbers, can be utilized to trigger a mechanism in cells for therapeutic and diagnostic (theragnostic) purposes. Among other metal nanoparticles that have been extensively studied for such purposes, gold nanoparticles, such as hollow gold nanostructures (HGNs), emerge as ideal tools for these applications since they possess optical tunability, easy functionalization, inertness, non-toxic behavior, accumulation in tissues, and intense absorption of NIR light. During the NIR absorption process, the absorbed energy by HGNs will be transferred into thermal energy that consequently heats the surroundings. This NIR mediated heating process can be employed for thermal cleavage of chemical bonds within the molecules, so called “thermolabile caged compounds”. This project proposes a novel design and synthesis of NIR driven thermolabile caged molecules as a nano-scale delivery tool, and their self-assembly on HGNs for targeted therapy and optical imaging applications.'

Introduzione (Teaser)

Release of therapeutic molecules in vitro upon exposure to near-infrared (NIR) light has been successfully employed to kill cancer cells. It opens the door to deep-tissue diagnostics and treatments with minimal tissue damage.

Descrizione progetto (Article)

Scientists largely focused on the use of ultraviolet (UV) light to release bound molecules from carriers and treat biological targets with spatial and temporal sensitivity. However, UV light does not penetrate deep tissues as required for many therapeutic or diagnostic (theragnostic) applications. In addition, it is strongly absorbed, causing undesirable destruction. Both have hampered its applicability in vivo.

EU-funded scientists working on the project 'Self-assembled thermo-nanoprobes on hollow gold nanoparticles for theragnostic applications' (TNP-HGNS) overcame these significant challenges. They exploited NIR radiation known to penetrate deeply with minimal absorption and hollow gold and silver nanostructures such as cubes, cages and spheres to deliver the theragnostic molecules.

Gold and silver accumulate in tissues and intensely absorb NIR light, are optically tuneable and easily functionalised. They are well-suited to biological applications due to their lack of reactivity or toxicity. When these hollow metal nanostructures absorb NIR radiation, the resulting thermal energy cleaves chemical bonds in the thermolabile (changing in composition in response to heat) caged compounds.

Researchers developed the routes to synthesise and functionalise gold and silver thermolabile nanostructures first with dye as a test and then with the cancer drug doxorubicin (Dox). They tested their ability to release the Dox and decrease the viability of MCF7 breast cancer cells (in vitro).

Both with continuous-wave and nanosecond pulse laser irradiation, there was a clear decrease in cell viability. With a two-Watt continuous-wave source, approximately half the cells were killed. More than 80% of cancerous cells were killed with the 320 milliWatt (mW) nanosecond pulse laser source.

Optical release of molecules in vivo for targeted theragnostics holds great promise. TNP-HGNS successfully delivered novel NIR-driven release technology with demonstrated effects on the viability of cancer cells in vitro.

The study is truly a breakthrough and paves the way to further research for eventual testing in clinical trials to pioneer developments in the diagnosis and treatment of important diseases. Thirteen publications ensure the outcomes reach a broad scientific community.