In cancer treatment, nanomedicines may be employed in an attempt to improve the tumor localization of antineoplastic drugs e.g. immunotherapeutic agents either through passive or active targeting,... Show moreIn cancer treatment, nanomedicines may be employed in an attempt to improve the tumor localization of antineoplastic drugs e.g. immunotherapeutic agents either through passive or active targeting, thereby potentially enhancing therapeutic effect and reducing undesired off-target effects. However, a large number of administrated nanocarriers often fail to reach the tumor area. In the present study, we show that photodynamic therapy (PDT) enhances the tumor accumulation of systemically administered lipid-PEG layer coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP). Intravital microscopy and histological analysis of the tumor area reveal that the tumor vasculature was disrupted after PDT, disturbing blood flow and coinciding with entrapment of nanocarriers in the tumor area. We observed that the nanoparticles accumulating after treatment do not confine to specific locations within the tumor, but rather localize to various cells present throughout the tumor area. Finally, we show by flow cytometry that NP accumulation occurred mostly in immune cells of the myeloid lineage present in the tumor microenvironment (TME) as well as in tumor cells, albeit to a lower extent. These data expose opportunities for combination treatments of clinical PDT with NP-based immunotherapy to modulate the TME and improve antitumor immune responses. Show less
The biological application of photoactivatable ruthenium anticancer prodrugs is limited by the need to use poorly penetrating high-energy visible light for their activation. Upconverting... Show moreThe biological application of photoactivatable ruthenium anticancer prodrugs is limited by the need to use poorly penetrating high-energy visible light for their activation. Upconverting nanoparticles (UCNPs), which produce high-energy light under near-infrared (NIR) excitation, can solve this issue, provided that they form stable, water (H2O)-dispersible nano-conjugates with the prodrug and that there is efficient energy transfer from the UCNP to the ruthenium complex. Herein, we report on the synthesis and photochemistry of the ruthenium(II) polypyridyl complex [Ru(bpy)(2)(3(H))](PF6)(2) ([1](PF6)(2)), where bpy = 2,2-bipyridine and 3(H) is a photocleavable bis(thioether) ligand modified with two phosphonate moieties. This ligand was coordinated to the ruthenium center through its thioether groups and could be dissociated under blue-light irradiation. Complex [1](PF6)(2) was bound to the surface of NaYF4:Yb3+,Tm3+@ NaYF4:Nd3+@NaYF4 core-shell-shell (CSS-)UCNPs through its bis(phosphonate) group, thereby creating a H2O-dispersible, thermally stable nanoconjugate (CSS-UCNP@[1]). Conjugation to the nanoparticle surface was found to be most efficient in neutral to slightly basic conditions, resulting in up to 2.4 x 10(3) Ru-II ions per UCNP. The incorporation of a neodymium-doped shell layer allowed for the generation of blue light using low-energy, deep-penetrating light (796 nm). This wavelength prevents the undesired heating seen with conventional UCNPs activated at 980 nm. Irradiation of CSS-UCNP@[1] with NIR light led to activation of the ruthenium complex [1](PF6)(2). Although only one of the two thioether groups was dissociated under irradiation at 50 W.cm(-2), we provide the first demonstration of the photoactivation of a ruthenium thioether complex using 796 nm irradiation of a H2O-dispersible nanoconjugate. Show less
Gold nanoparticles show surprisingly strong interactions with light in the visible range, which can be divided into scattering, absorption, and photoluminescence. When a nanoparticle absorbs light,... Show moreGold nanoparticles show surprisingly strong interactions with light in the visible range, which can be divided into scattering, absorption, and photoluminescence. When a nanoparticle absorbs light, the corresponding energy is converted to heat, which can affect the environment of the (hot) nanoparticle. This thesis uses scattering and photoluminescence to study the behaviour of optically heated single gold nanoparticles: it discusses the behaviour of single plasmonic vapour nanobubbles, which occur around highly heated nanoparticles immersed in a liquid, the detection of chirality in nano-objects through their absorption and the photothermal effect, the behaviour of gold nanoparticles under sub-picosecond pulsed excitation, and the temperature dependence of pulse-excited photoluminescence of such particles. Show less
