Xiaoqiang Qiao,Yanjun Yang,Shijia Liu,Shiheng Chen,Xin Wang,Guangyue Li,Hongyuan Yan,Xun Yang
In this study, a novel type of pyridinium-based tags, 1-[3-[(2-iodo-1-oxoethyl)amino]propyl]-4-methylpyridinium bromide (IMP) and 1-[3-[(2-iodo-1-oxoethyl)amino]propyl]-4-propylpyridinium bromide (IPP), were designed, synthesized, and applied to the derivatization of thiol-containing peptides. With model peptides as the sample, the labeling efficiency and the stability of the peptide derivatives were investigated. The results indicate that nearly 100% derivatization yield was achieved with the developed tags and the peptide derivatives were stable at room temperature for at least one week. Furthermore, improved ionization efficiency and increased charge states were achieved via both matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) and electrospray ionization (ESI) MS, of which IPP exhibited the more obvious improvement of ionization efficiency. Further analysis of tryptic digests of bovine serum albumin (BSA) and α-transferrin, showed that increased identification efficiency of the thiol-containing peptides was achieved by combination with IMP or IPP derivatization. For example, the identification efficiency of the thiol-containing peptides of α-transferrin increased more than 42% upon combination with the IMP or IPP derivatives. We anticipate the novel tags are promising for highly efficient thiol-containing peptide identification in proteome research, especially for low concentrations.
Background Radionuclides have important roles in clinical tumor radiotherapy as they are used to kill tumor cells or as imaging agents for drug tracing. The application of radionuclides has been developing as an increasing number of nanomaterials are used to deliver radionuclides to tumor areas to kill tumor cells. However, promoting the efficient combination of radionuclides and nanocarriers (NCs), enhancing radionuclide loading efficiency, and avoiding environmental pollution caused by radionuclide overuse are important challenges that hinder their further development.Methods In the present study, a new small molecule compound (3-[[(2S)-2-hydroxy-3-(4-hydroxyphenyl)-1-carbonyl] amino]-alanine, abbreviation: HN, molecular formula: C12H16N2O5) was synthesized as a linker between radionuclide iodine-125 (125I) and NCs to enable a more efficient binding between NCs and radionuclides.Results In vitro evidence indicated that the linker was able to bind 125I with higher efficiency (labeling efficiency >80%) than that of tyrosine, as well as various NCs, such as cellulose nanofibers, metal oxide NCs, and graphene oxide. Single-photon emission computed tomography/computed tomography imaging demonstrated the biological distribution of 125I-labeled NCs in different organs/tissues after administration in mice.Conclusion These results showed an improvement in radionuclide labeling efficiency for nanocarriers and provided an approach for nanocarrier image tracing.
Haidong Shen,Surui Chen,Chonghai Zhang,Teng Liu,Yugui Tao,Lin Hu,Kai Yang
Radioisotope therapy (RIT) is one of clinical treatment for tumors, which can not only directly kill tumor cells, but also enhance anti-tumor immune response by inducing tumor cell immunogenic cell death (ICD). However, significant challenges for RIT are the low radiolabeling efficiency, as well as tumor targeting issues. Bacterial outer membrane vesicles (OMVs), which are natural nano-vesicles secreted by Gram-negative bacteria, are now garnering significant attention in cancer therapy due to their tumor-targeting and immunotherapeutic potential. Herein, we construct an engineering delivery platform based on OMVs to achieve efficient labeling of radioactive iodine and improve radio-immunotherapy ( 131 I-STATH-OMV-PEG). Firstly, high tyrosine-rich protein statherin (STATH) is integrated onto the surface of OMVs (STATH-OMV) through bioengineered technology. The obtained STATH-OMV is coated with polyethylene glycol (PEG) and then labeled with radionuclide iodine-131 ( 131 I-STATH-OMV-PEG), which exhibit excellent radiolabeling efficiency due to the integration of STATH. More importantly, 131 I-STATH-OMV-PEG could also boost DC maturation and produce anti-tumor cytokines, thereby enhancing the systemic anti-tumor immune response induced by RIT. Additionally, 131 I-STATH-OMV-PEG could inhibit orthotopic colon cancer, induce systemic immune memory effect and prevent tumor invasion. In summary, this study proposes an OMV-centered RIT delivery system that ensures proficient labeling of 131 I, thereby amplifying the therapeutic effect of RIT and opening up a promising approach for tumor radio-immunotherapy.
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