Abstract
193mPt and 195mPt radionuclides are therapeutically attractive Auger electron emitters with notably high Auger electron yield per decay. The present paper summarizes the first step of research on the applications of core-shell (Au@Pt) nanoparticles for electron Auger therapy of HER2+ (human epidermal growth factor receptor 2) breast cancer and hepatocellular carcinoma. Gold nanoparticles (30 nm) were synthesized covered with a platinum shell at high efficiency (>80%) and were further evaluated for in vitro studies such as binding affinity, internalization and cytotoxicity. To find the mechanism(s) responsible for platinum cytotoxicity in HepG2 cells, the platinum concentration in isolated cell nuclei and cytoplasm was determined using ICP-MS (inductively coupled plasma mass spectrometry). Lack of platinum in cell nuclei suggests that the cytotoxic effect is associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Studies carried out on the SKOV-3 cell line with the use of a synthesized targeting bioconjugate (Au@Pt-PEG-trastuzumab) revealed a high affinity of this preparation to HER2+ cells, its internalization, its placement in the perinuclear area and partial intranuclear location. The specific binding for HER2 negative cells, MDA-MB-231, was negligible and Au@Pt-PEG-trastuzumab did not enter these cells. The results obtained are promising and warrant future investigation of Auger electron therapy using 193mPt and 195mPt based radiopharmaceuticals.
Highlights
In the last decade, there has been great emphasis on “targeted therapies” that are designed to kill cancer cells selectively, leaving healthy tissues unaffected
Au@Pt-PEG-trastuzumab and Au@Pt-PEG-COOH conjugates were studied in terms of their application as radioactive analogues labeled with 193m,195mPt
The performed studies have shown that Au@Pt-PEG-trastuzumab exhibits a high affinity to HER2 receptors, over 90% internalization and location in the perinuclear area. tested concentrations, cytotoxicity of the conjugate was not observed
Summary
There has been great emphasis on “targeted therapies” that are designed to kill cancer cells selectively, leaving healthy tissues unaffected. One such therapy is targeted radionuclide therapy (TRT) in which cancer cells are killed as a result of corpuscular radiation emitted by radionuclides conjugated to biological molecules that bind to the surface of specific cancer cells. The specificity of binding is affected by the recognition of surface receptors or other proteins overexpressed by cancer cells Such a selective mechanism of radiation delivery minimizes toxicity to the surrounding normal tissues. In the case of small tumors and cancer metastasis treatment, remarkable therapeutic results have been achieved recently with the use of targeting molecules labeled with emitters of short distance corpuscular radiation like α and Auger electron particles [1,2]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call