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SUMMARY:193m\,195mPt-based nanobioconjugates for combined „chemo-Auger
 ” theranostics of hepatocellular carcinoma (HCC) and HER2+ breast cancer
 .
DTSTART;VALUE=DATE-TIME:20211011T101000Z
DTEND;VALUE=DATE-TIME:20211011T103000Z
DTSTAMP;VALUE=DATE-TIME:20260904T172136Z
UID:indico-contribution-246@indico.koza.if.uj.edu.pl
DESCRIPTION:Speakers: Kamil Wawrowicz (Institute of Nuclear Chemistry and 
 Technology\, Dorodna 16\, 03-195 Warsaw\, Poland)\nDespite the broad devel
 opment of medicine for cancer treatment\, current therapeutic approaches a
 re not efficient at dealing with aggressive and therapy-resistant neoplasm
 s such as breast cancer or hepatocellular carcinoma. In these tumors\, one
  of the most difficult steps of the therapy process is metastases treatmen
 t due to the spread of small size tumors. Targeted therapy with most effic
 ient Auger electrons emitters – 193mPt (30 A.E. per decay) and 195mPt (3
 6 A.E. per decay) - is one of the most promising concept for this approach
 . Moreover\, 195mPt can be easily imaged via SPECT as a result of emission
  suitable for imaging photons with energy ~98.90 keV. Platinum-based radio
 pharmaceuticals\, due to their relevant characteristics\, are encouraging 
 candidates for realizing “chemo-Auger” therapy which should be signifi
 cantly more effective than typical Auger therapy. Chemotoxicity of platinu
 m can be promoted in highly oxidative environment which occurs in most of 
 hepatic cells and in some of breast/ovarian cancer cells. Biological effec
 tiveness studies of platinum-induced chemotoxicity were realized with two 
 types of nanocarriers – 30 nm core-shell (Au@Pt) and ultra-small 2 nm pl
 atinum (PtNPs) nanoparticles\, used in forms of HER2+ targeted bioconjugat
 es with Trastuzumab\, as well as only polymer-stabilized conjugates for HC
 C. Research for non-radioactive (bio)conjugates chemotoxicity included eva
 luation for 2D and 3D in vitro tumor spheroid models. Moreover\, one of th
 e main parts was aimed at determining the mechanism of chemotoxicity. Ther
 e are two different concepts of platinum biological activity. In order to 
 identify the factors responsible for cytotoxic effects\, nuclei isolation 
 and oxidative stress markers determination were performed. Obtained result
 s confirmed\, that for chemotoxicity of platinum-based nanomaterials\, hig
 hly oxidative environment is a crucial parameter. Due to presence of natur
 ally occurring increased H2O2 concentration in HCC cells cytoplasm\, in th
 is cancer cells significant cytotoxicity was observed at similar level for
  both - Au@Pt and PtNPs conjugates (~50% at 72h post treatment). Furthermo
 re\, our results strongly indicates\, that in HER2 overexpressed breast/ov
 arian cancer cells the oxidative potential is insufficient for inducing cy
 totoxic effects of platinum. After widely conducted chemical and biologica
 l research for non-radioactive conjugates\, evaluation with radioactive 19
 3m\,195mPt will be performed. Due to very limited availability of high spe
 cific activity Pt radionuclides\, during subsequent part of research\, var
 ious direct and indirect ways for high specific activities production will
  be under investigation.\nThis research was funded by National Science Cen
 tre (NCN)\, grant number UMO-2019/35/B/ST4/01433 (OPUS)”. The contributi
 on of PhD student Kamil Wawrowicz was realized within Project No. POWR.03.
 02.00-00-I009/17-00 (Operational Project Knowledge Education Development 2
 014–2020 co-financed by European Social Fund).\n\nhttps://indico.koza.if
 .uj.edu.pl/event/4/contributions/246/
LOCATION:Theranostics Center / on-line
URL:https://indico.koza.if.uj.edu.pl/event/4/contributions/246/
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