Liposomes have been well established as an effective drug delivery system, due to simplicity of their preparation and unique characteristics. However conventional liposomes are unsuitable for the on-demand content release, which limits their therapeutic utility. Here we report X-ray-triggerable liposomes incorporating gold nanoparticles and photosensitizer verteporfin. The 6 MeV X-ray radiation induces verteporfin to produce singlet oxygen, which destabilises the liposomal membrane and causes the release of cargos from the liposomal cavity. This triggering strategy is demonstrated by the efficiency of gene silencing in vitro and increased effectiveness of chemotherapy in vivo. Our work indicates the feasibility of a combinatorial treatment and possible synergistic effects in the course of standard radiotherapy combined with chemotherapy delivered via X-ray-triggered liposomes. Importantly, our X-ray-mediated liposome release strategy offers prospects for deep tissue photodynamic therapy, by removing its depth limitation.

We discuss the phenomenon of enhanced fluorescence in the proximity of metal nanostructures addressing the question of how much fluorescence signal can be obtained from fluorophores in such altered environments. We review its applicability for the methodologies used in the life science, such as immunoassays, flow cytometry and bioimaging. Experimental and theoretical scenarios employing various metal nanostructures - such as homogeneous enhancing substrates, fluorescence-enhancing microbeads, and metal core-dielectric shell nanocomposites - are described.

Singlet oxygen is a primary cytotoxic agent in photodynamic therapy. We show that CeF3 nanoparticles, pure as well as conjugated through electrostatic interaction with the photosensitizer verteporfin, are able to generate singlet oxygen as a result of UV light and 8 keV X-ray irradiation. The X-ray stimulated singlet oxygen quantum yield was determined to be 0.79 ± 0.05 for the conjugate with 31 verteporfin molecules per CeF3 nanoparticle, the highest conjugation level used. From this result we estimate the singlet oxygen dose generated from CeF3-verteporfin conjugates for a therapeutic dose of 60 Gy of ionizing radiation at energies of 6 MeV and 30 keV to be (1.2 ± 0.7) × 108 and (2.0 ± 0.1) × 109 singlet oxygen molecules per cell, respectively. These are comparable with cytotoxic doses of 5 × 107–2 × 109 singlet oxygen molecules per cell reported in the literature for photodynamic therapy using light activation. We confirmed that the CeF3-VP conjugates enhanced cell killing with 6 MeV radiation. This work confirms the feasibility of using X- or γ- ray activated nanoparticle-photosensitizer conjugates, either to supplement the radiation treatment of cancer, or as an independent treatment modality.

The development of vaccines against specific types of cancers will offer new modalities for therapeutic intervention. Here we describe the synthesis of a novel vaccine construction prepared from spherical gold nanoparticles of 3–5 nm core diameters. The particles were coated with both the tumor-associated glycopeptides antigens containing the cell-surface mucin MUC4 with Thomsen Friedenreich (TF) antigen attached at different sites and a 28-residue peptide from the complement derived protein C3d to act as a B-cell activating “molecular adjuvant”. The synthesis entailed solid phase glycopeptide synthesis, design of appropriate linkers and attachment chemistry of the various molecules to the particles. Attachment to the gold surface was mediated by a novel thiol-containing 33 atom linker which was further modified to be included as a third “spacer” component in the synthesis of several three-component vaccine platforms. Groups of mice were vaccinated either with one of the nanoplatform constructs or with control particles without antigen coating. Evaluation of sera from the immunized animals in enzyme immunoassays (EIA) against each glycopeptide antigen showed a small but statistically significant immune response with production of both IgM and IgG isotypes. Vaccines with one carbohydrate antigen (B, C and E) gave more robust responses than the one with two contiguous disaccharides (D), and vaccine E with a TF antigen attached to threonine at the 10th position of the peptide was selected for IgG over IgM suggesting isotype switching. The data suggested that this platform may be a viable delivery system for tumor-associated glycopeptide antigens.