This paper reports on the development of tumor-specific gold nanoparticles (AuNPs) as theranostic tools intended for target accumulation and the detection of tumor angiogenesis via optical imaging (OI) before therapy is performed, being initiated via an external X-ray irradiation source. The AuNPs were decorated with a near-infrared dye, and RGD peptides as the tumor targeting vector for α_vβ₃-integrin, which is overexpressed in tissue with high tumor angiogenesis. The AuNPs were evaluated in an optical imaging setting in vitro and in vivo exhibiting favorable diagnostic properties with regards to tumor cell accumulation, biodistribution, and clearance. Furthermore, the therapeutic properties of the AuNPs were evaluated in vitro on pUC19 DNA and on A431 cells concerning acute and long-term toxicity, indicating that these AuNPs could be useful as radiosensitizers in therapeutic concepts in the future.

This paper reports on the development of stable tumor-specific gold nanoparticles (AuNPs) activated by neutron irradiation as a therapeutic option for the treatment of cancer with high tumor angiogenesis. The AuNPs were designed with different mono- or dithiol-ligands and decorated with different amounts of Arg-Gly-Asp (RGD) peptides as a tumor-targeting vector for α_vβ₃ integrin, which is overexpressed in tissues with high tumor angiogenesis. The AuNPs were evaluated for avidity in vitro and showed favorable properties with respect to tumor cell accumulation. Furthermore, the therapeutic properties of the [¹⁹⁸Au]AuNPs were evaluated in vitro on U87MG cells in terms of cell survival, suggesting that these [¹⁹⁸Au]AuNPs are a useful basis for future therapeutic concepts.

Recently, anionic charges were found to negatively influence the in vitro gastrin-releasing peptide receptor (GRPR) binding parameters of dually radioisotope and fluorescent dye labeled GRPR-specific peptide dimers. From this, the question arose if this adverse impact on in vitro GRP receptor affinities could be mitigated by a higher valency of peptide multimerization. For this purpose, we designed two different hybrid multimodal imaging units (MIUs), comprising either one or two click chemistry-compatible functional groups and reacted them with PESIN (PEG₃-BBN_7–14, PEG = polyethylene glycol) dimers to obtain a dually labeled peptide homodimer or homotetramer. Using this approach, other dually labeled peptide monomers, dimers, and tetramers can also be obtained, and the chelator and fluorescent dye can be adapted to specific requirements. The MIUs, as well as their peptidic conjugates, were evaluated in terms of their photophysical properties, radiolabeling efficiency with ⁶⁸Ga and ⁶⁴Cu, hydrophilicity, and achievable GRP receptor affinities. Here, the hydrophilicity and the GRP receptor binding affinities were found to be especially strongly influenced by the number of negative charges and peptide copies, showing log_D (1-octanol-water-distribution coefficient) and IC₅₀ (half maximal inhibitory concentration) values of −2.2 ± 0.1 and 59.1 ± 1.5 nM for the homodimer, and −1.9 ± 0.1 and 99.8 ± 3.2 nM for the homotetramer, respectively. From the obtained data, it can be concluded that the adverse influence of negatively charged building blocks on the in vitro GRP receptor binding properties of dually labeled PESIN multimers can, at least partly, be compensated for by the number of introduced peptide binding motives and the used molecular design.

Objectives: This paper reports the preclinical evaluation of stable tumor-specific gold nanoparticles (AuNPs) activated by neutron irradiation as a therapeutic option for the treatment of cancers characterized by high tumor angiogenesis. Methods: A selection of promising AuNPs with high avidity to α_vβ₃-expressing glioma (U-87 MG) cells (IC₅₀ = 82–104 nM) were chosen with different surface loading of Arg-Gly-Asp (RGD) peptides as tumor targeting vectors for integrin α_vβ₃, a target which is overexpressed in tissues displaying high tumor angiogenesis. Three different [¹⁹⁸Au]AuNPs were evaluated applying three injection methods, intravenous (i.v.), intraperitoneal (i.p.), and intratumoral (i.t.), each in a group of six U-87 MG xenograft–bearing mice (54 female athymic nude mice in total). Their biodistribution and tumor accumulation was assessed by in vivo imaging within 1–7 days after injection and 7 days after injection by ex vivo measurement. Results: The developed [¹⁹⁸Au]AuNPs exhibited suboptimal biodistribution by i.v. application (accumulation pattern tail > liver > spleen, no significant tumor accumulation) and by i.p. application (accumulation pattern spleen >> liver > pancreas, slight tumor accumulation of <0.3 %ID/g). However, an acceptable biodistribution by i.t. application was observed (5.5 %ID/g in liver, 4.9 %ID/g in spleen, and 3.0 %ID/g in tumor). Conclusions: Despite the very promising in vitro results, the in vivo evaluation suggests that the [¹⁹⁸Au]AuNPs represent a platform for the development of restricted therapeutic strategies.