Page 236 - Haematologica March 2020

A. Falgàs et al.
ing) was observed in the BM of T22-DITOX-H6-treated of the nanocarrier under examination to efficiently deliver mice (Figure 8C). Lastly, we did not find any macroscopic antitumor agents to achieve the selective killing of CXCR4+ (datanotshown)ormicroscopic(H&Estaining)alterationin lymphoma cells without inducing toxicity on CXCR4+ liver and kidneys (Figure 8D). Our results support the use mouse hematopoietic cells or systemic organs.
Figure 8. Evaluation of T22-DITOX-H6 antitumor effect and toxicity in a CXCR4+ subcutaneous (SC) Toledo mouse model. (A) Apoptosis detection by cleaved Poly(ADP-ribose) polymerase (PARP) immunohistochemistry (IHC) as well as nuclear condensation by 4′,6-diamidino-2-phenylindole (DAPI) staining. (B) Mean quan- tification of cleaved PARP stained area (above) and number of apoptotic bodies by DAPI staining (bottom) in SC Toledo tumors 24 hours (h) after treatment with buffer or a single intravenous (IV) injection of 25 mg T22-DITOX-H6. (C) Lack of T22-DITOX-H6-induced toxicity in mouse bone marrow (BM). Human anti-CD20 and mouse anti-CXCR4 IHC assays were used to identify CXCR4+ mouse cells resident in BM. Hematoxylin & Eosin (H&E) and DAPI staining samples were examined to detect possible alterations in cell morphology or cell death induction. (D) Lack of systemic toxicity in liver or kidney by histological analysis of tissue sections H&E 24h after treatment with buffer or 25 mg T22-DITOX-H6. All images were taken at x400 and inserts at x1000. *P<0.05.
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