Thesis (M.Sc.)-Cairo University, 2023.

Bibliography: pages 119-131.

Currently, the main therapies for treating cancer are associated with a variety of side effects.
Accordingly, researchers are focusing on the use of nanotherapy to develop a highly novel, less toxic
and extremely efficient therapeutic agents for cancer treatment. Silver doped Hydroxyapatite
nanoparticles (Ag:HAp-NPs) have shown effective at treating both infections and cancerous tumors
while being non- cytotoxic to normal healthy cells in vitro. Therefore, this study was undertaken to
estimate the safety and anti-tumor activity of silver doped hydroxyapatite nanoparticles in mice in
vivo. Regarding the antitumor activity, concurrent administration of Ag:HAp-NPs caused a
significant decrease in tumor volume and weight. Additionally, it showed a high elevation of
intracellular ROS generation as well as MDA levels within tumor tissues and lead to the induction
of DNA breaks. The high production of intracellular ROS generation, and the oxidative stress
induction by Ag:HAp-NPs within tumor tissues confirmed a decrease in GSH and GPx levels.
Significant elevation of P53 and HO-1 gene and decrease in Hsp70 and Kras was observed as well.
Additionally, the percentage of necrotic tissue in tumor- induced groups and % of degenerated tumor
cells after treatment with Ag:HAp-NPs were significantly elevated. Regarding the safety of Ag:HAp-
NPs, it was shown to be safe and non-genotoxic. This was confirmed by the non-significant changes
in TL and TM in the bone marrow and liver tissues. It was further confirmed by the observed non-
significant changes in the MDA and TAC levels as well as the SOD activity in the liver among the
safety groups, except for high dosage level. Moreover, histological examinations demonstrated that
Silver doped Hydroxyapatite nanoparticles have mild toxicity on kidney and liver tissues with
minimal inflammatory reactions associated with the presence of Ag:HAp-NPs in contrast with
Cisplatin. In conclusion, silver doped hydroxyapatite nanoparticles have a potential anticancer
activity against induced solid tumors in mice and demonstrated a higher level of safety for the liver,
kidney and bone marrow tissues, making Ag:HAp-NPs a promising anti-tumor agent.

ﺣﺎﻟًﯿﺎ،ﺗﺮﺗﺒﻂ اﻟﻌﻼﺟﺎت اﻟﺮﺋﯿﺴﯿﺔ ﻟﻌﻼج اﻟﺴﺮطﺎن ﺑﻤﺠﻤﻮﻋﺔ ﻣﺘﻨﻮﻋﺔﻣﻦاﻵﺛﺎر اﻟﺠﺎﻧﺒﯿﺔ.وﻓًﻘﺎ ﻟﺬﻟﻚ،ﯾﺮﻛﺰا ﻟﺒﺎﺣﺜﻮن ﻋﻠﻰ
اﺳﺘﺨﺪام اﻟﻌﻼج ﺑﺎﻟﻨﺎﻧﻮ ﻟﺘﻄﻮﯾﺮ ﻋﻮاﻣﻞ ﻋﻼﺟﯿﺔ ﺟﺪﯾﺪة ﻟﻠﻐﺎﯾﺔ ؤاﻗﻞ ﺳﻤﯿﺔ وﻓﻌﺎﻟﺔ ﻟﻠﻐﺎﯾﺔ ﻟﻌﻼج اﻟﺴﺮطﺎن.ٔاظﮭﺮت ﺟﺰﯾﺌﺎت
ھﯿﺪروﻛﺴﯿﺒﺎﺗﯿﺖ اﻟﻨﺎﻧﻮﯾﺔ اﻟﻤﻄﻌﻤﺔ ﺑﺎﻟﻔﻀﺔ)Ag: HAp-NPs( ﻓﻌﺎﻟﯿﺘﮭﺎ ﻓﻲ ﻋﻼج ﻛﻞ ﻣﻦ اﻻﻟﺘﮭﺎﺑﺎت واﻷورام اﻟﺴﺮطﺎﻧﯿﺔ
ﺑﯿﻨﻤﺎ ﺗﻜﻮن ﻏﯿﺮﺳﺎﻣﺔ ﻟﻠﺨﻼﯾﺎ اﻟﺴﻠﯿﻤﺔ ﻣﻌﻤﻠﯿﺎ in vitro .ﻟﺬﻟﻚ،ٔ اﺟﺮﯾﺖ ھﺬه اﻟﺪراﺳﺔ ﻟﺘﻘﺪﯾﺮ اﻟﺴﻼﻣﺔ واﻟﻨﺸﺎط اﻟﻤﻀﺎد ﻟﻠﻮرم
ﻣﻦ ﻟﺠﺴﯿﻤﺎت ھﯿﺪروﻛﺴﯿﺒﺎﺗﯿﺖ اﻟﻨﺎﻧﻮﯾﺔ اﻟﻤﻄﻌﻤﺔ ﺑﺎﻟﻔﻀﺔ ﻓﻲ اﻟﻔﺌﺮان ﻓﻲ اﻟﺠﺴﻢ اﻟﺤﻲ in vivo .ﻓﯿﻤﺎ ﯾﺘﻌﻠﻖ ﺑﺎﻟﻨﺸﺎط اﻟﻤﻀﺎد
ﻟﻠﻮرم، ﺗﺴﺒﺐ اﻹ ﻋﻄﺎء اﻟﻤﺘﺰاﻣﻦ ﻟـ Ag: HAp-NPs ﻓﻲ اﻧﺨﻔﺎض ﻛﺒﯿﺮ ﻓﻲ ﺣﺠﻢ ووزن اﻟﻮرم. ﺑﺎﻹﺿﺎﻓﺔٕ اﻟﻰ ذﻟﻚ اظﮭﺮ
ارﺗﻔﺎﻋﺎ ﻛﺒیرا ﻓﻲﺗﻮﻟﯿﺪ ROSداﺧﻞ اﻟﺨﻼﯾﺎ وﻛﺬﻟﻚ ﻣﺴﺘﻮﯾﺎتMDA داﺧل أﻧﺴﺠﺔ اﻟﻮرم وﯾٔﻮديٕ اﻟﻰ ﺗﺤﺮﯾﺾ ﻓﻮاﺻﻞ
اﻟﺤﻤﺾاﻟﻨﻮوي.ٔ اﻛﺪ اﻹﻧﺘﺎج اﻟﻌﺎﻟﻲﻟﺘﻮﻟﯿﺪ ROS داﺧﻞ اﻟﺨﻼﯾﺎ، وﺗﺤﺮﯾﺾ اﻹﺟﮭﺎد اﻟﺘﺄﻛﺴﺪي ﺑﻮاﺳﻄﺔ Ag: HAp-NPs
داﺧﻞٔ اﻧﺴﺠﺔاﻟﻮرم اﻧﺨﻔﺎﺿا ﻓﻲ ﻣﺴﺘﻮﯾﺎت GSHو.GPxﻛﻤﺎ ﻟﻮﺣﻆ ارﺗﻔﺎع ﻛﺒﯿﺮ ﻓﻲ ﺟﯿﻦP53وHO-1واﻧﺨﻔﺎضﻓﻲ
Hsp70وKras.ﺑﺎﻹﺿﺎﻓﺔٕ اﻟﻰذﻟﻚ،ﺗﻢ رﻓﻊ ﻧﺴﺒﺔ اﻷﻧﺴﺠﺔ اﻟﻤﯿﺘﺔ ﻓﻲ اﻟﻤﺠﻤﻮﻋﺎت اﻟﺘﻲ ﯾﺴﺒﺒﮭﺎ اﻟﻮرم وﻧﺴﺒﺔ اﻟﺨﻼﯾﺎ
اﻟﺴﺮطﺎﻧﯿﺔاﻟﻤﺘﺪھﻮرةﺑﻌﺪاﻟﻌﻼج Ag: HAp-NPsﺑﺸﻜﻞﻣﻠﺤﻮظ.ﻓﯿﻤﺎﯾﺘﻌﻠﻖﺑﺴﻼﻣﺔ :Ag HAp-NPs،ﻓﻘﺪﺛﺒﺖٔ اﻧﮭﺎ
ٓاﻣﻨﺔوﻏﯿﺮﺳﺎﻣﺔﻟﻠﺠﯿﻨﺎت.ﺗﻢﺗﺄﻛﯿﺪذﻟﻚﻣﻦﺧﻼل اﻟﺘﻐﯿﯿﺮات ﻏﯿﺮاﻟﻤﮭﻤﺔﻓﻲTLوTMﻓﻲﻧﺨﺎع اﻟﻌﻈﺎم ؤاﻧﺴﺠﺔاﻟﻜﺒﺪ.ﺗﻢ
ﺗﺄﻛﯿﺪذﻟﻚٔای ًﺿﺎﻣﻦ ﺧﻼل اﻟﺘﻐﯿﯿﺮات ﻏﯿﺮاﻟﻤﻠﺤﻮظﺔ ﻓﻲﻣﺴﺘﻮﯾﺎت MDAوTACﺑﺎﻹﺿﺎﻓﺔٕ اﻟﻰﻧﺸﺎطSODﻓﻲاﻟﻜﺒﺪ

Issues also as CD.

Text in English and abstract in Arabic & English.