Additional file 2: of Optical imaging of pre-invasive breast cancer with a combination of VHHs targeting CAIX and HER2 increases contrast and facilitates tumour characterization

Signal bleeding. Each fluorescent VHH is detected by one channel only of the imaging system. (4.16 MB

Additional file 1: of Optical imaging of pre-invasive breast cancer with a combination of VHHs targeting CAIX and HER2 increases contrast and facilitates tumour characterization

Supplementary methods and figures. Figure 1S: SDS-PAGE analysis of NIR fluorescent VHHs. Figure 2S: Total fluorescence intensity of 11A4-800 and 11A4-680 at the tumour and in the background area obtained 5 h p.i. during the ex vivo tumour imaging. (34.9 MB

Inhibition of Tumor Growth by Targeted Anti-EGFR/IGF-1R Nanobullets Depends on Efficient Blocking of Cell Survival Pathways

The clinical efficacy of epidermal growth factor receptor (EGFR)-targeted inhibitors is limited due to resistance mechanisms of the tumor such as activation of compensatory pathways. Crosstalk between EGFR and insulin-like growth factor 1 (IGF-1R) signaling has been frequently described to be involved in tumor proliferation and resistance. One of the attractive features of nanomedicines is the possibility to codeliver agents that inhibit different molecular targets in one nanocarrier system, thereby strengthening the antitumor effects of the individual agents. Additionally, exposure to healthy tissues and related unwanted side-effects can be reduced. To this end, we have recently developed anti-EGFR nanobody (Nb)-liposomes loaded with the anti-IGF-1R kinase inhibitor AG538, which showed promising antiproliferative effects in vitro. In the present study, we have further evaluated the potential of this dual-active nanomedicine in vitro and for the first time in vivo. As intended, the nanomedicine inhibited EGFR and IGF-1R signaling and subsequent activation of downstream cell proliferation and survival pathways. The degree of inhibition induced by the nanomedicine on a molecular level correlated with cytotoxicity in tumor cell proliferation assays and may even be predictive of the response to nanomedicine treatment in tumor xenograft models. Combination therapy with kinase inhibitor-loaded Nb–liposomes is therefore an appealing strategy for inhibiting the proliferation of tumors that are highly dependent on EGFR and IGF-1R signaling

In vitro bactericidal effect of 4497-IgG-IRDye700DX on implant colonized with S. aureus.

Different concentrations of the antibody-photosensitizer conjugate (0.1, 1.0 and 5.0 μg) and controls were used with a no treatment baseline control (black straight line with the ‘o’ symbol). Biofilms were irradiated with total light dose of 50J/cm2 after which Log (CFU/mL) was determined by serial dilution. 4497-IgG-IRDye700DX at 5 μg reduced S. aureus biofilm significantly. (CFU, colony-forming units).</p

CFU counts from implants and surrounded tissue taken from mice with an implant infection that were treated with 4497-IgG-IRDye700DX at two dosi and with various controls, including vancomycin.

The area around the implant was illuminated with a total light dose of 50J/cm2 after which CFU (Log) was determined by serial dilution on the implant (A) as well as in the tissue (B) around the implant. No significant difference in CFU was seen at the implants. In the tissue samples surrounding the implant, 4497-IgG-IRDye700DX at the highest dose of 400ug reduced S. aureus cells significantly compared to the other (control) groups.</p