Τίτλος:
Ag/Au bimetallic nanoparticles inhibit tumor growth and prevent metastasis in a mouse model
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Purpose: To evaluate the antitumor efficacy of Ag3Au1Trp1:2NPs in a SCID mouse cancer model, with respect to their effect on tumor growth, on tumor’s metastatic potential and the underlying molecular mechanism. Subjects and Methods: Ag3Au1Trp1:2NPs were radiolabeled with Gallium-68 and the biodistribution was studied in Swiss mice without tumors and in SCID mice bearing tumors. SCID mice received intratumoral Ag3Au1Trp1:2NPs and tumor size was measured using calipers. Lung and liver tissues were extracted and studied microscopically for the detection of any metastatic sites. Changes in the Caspase-3 and TNF-related apoptosis-inducing ligand (TRAIL) were also investigated using real-time PCR and Western blot techniques, respectively. Results: In the 4T1 tumor-bearing SCID mice, Ag3Au1Trp1:2NPs showed quick passive accumulation at tumor sites at 30 mins post-injection. Mice that received the highest dose of NPs (5.6mg/mL) demonstrated a 1.9-fold lower tumor volume compared to that of the control group at 11 days post-injection, while mice that did not receive NPs showed metastatic sites in liver and lung. Extracted tumor tissue of treated mice revealed increased Casp-3 mRNA levels as well as elevated TRAIL protein levels. Conclusion: Based on our results, Ag3Au1Trp1:2NPs express anti-tumor and anti-metastatic effects in vivo. Ag3Au1Trp1:2NPs also reach tumor site via the enhancement and retention effect which results in the apoptotic death of cancerous cells selectively via the extrinsic TRAIL-dependent pathway. © 2020 Katifelis et al.
Συγγραφείς:
Katifelis, H.
Mukha, I.
Bouziotis, P.
Vityuk, N.
Tsoukalas, C.
Lazaris, A.C.
Lyberopoulou, A.
Theodoropoulos, G.E.
Efstathopoulos, E.P.
Gazouli, M.
Περιοδικό:
International Journal of Nanomedicine
Εκδότης:
Dove Medical Press Ltd
Λέξεις-κλειδιά:
antimetastatic agent; antineoplastic agent; caspase 3; gallium 68; gold nanoparticle; messenger RNA; nanoparticle; silver nanoparticle; tryptophan nanoparticle; tumor necrosis factor related apoptosis inducing ligand; unclassified drug; antineoplastic agent; Casp3 protein, mouse; caspase 3; gallium; Gallium-68; gold; metal nanoparticle; silver; Tnfsf10 protein, mouse; tumor necrosis factor related apoptosis inducing ligand, animal experiment; animal tissue; antineoplastic activity; Article; cancer inhibition; controlled study; drug accumulation; drug clearance; drug distribution; female; liver; lung; metastasis inhibition; metastasis potential; mouse; nonhuman; protein expression; protein RNA binding; radioactivity; radiolabeling; real time polymerase chain reaction; tumor volume; Western blotting; animal; apoptosis; cell motion; chemistry; drug effect; experimental neoplasm; liver tumor; lung tumor; metabolism; pathology; SCID mouse; tissue distribution; tumor cell line, Animals; Antineoplastic Agents; Apoptosis; Caspase 3; Cell Line, Tumor; Cell Movement; Female; Gallium Radioisotopes; Gold; Liver Neoplasms; Lung Neoplasms; Metal Nanoparticles; Mice, SCID; Neoplasms, Experimental; Silver; Tissue Distribution; TNF-Related Apoptosis-Inducing Ligand; Tumor Burden