Details

Autor(en) / Beteiligte

• Naguib, Youssef W.
• Alhaj‐Suliman, Suhaila O.
• Wafa, Emad I.
• Saha, Sanjib
• Ebeid, Kareem
• Mohammed, Hamada H. H.
• Abdel‐Rahman, Somaya A.
• Abuo‐Rahma, Gamal El‐Din A.
• Geary, Sean M.
• Salem, Aliasger K.

Titel

Ciprofloxacin Derivative‐Loaded Nanoparticles Synergize with Paclitaxel Against Type II Human Endometrial Cancer

Ist Teil von

• Small (Weinheim an der Bergstrasse, Germany), 2024-10, Vol.20 (41), p.e2302931-n/a

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• Combinations of chemotherapeutic agents comprise a clinically feasible approach to combat cancers that possess resistance to treatment. Type II endometrial cancer is typically associated with poor outcomes and the emergence of chemoresistance. To overcome this challenge, a combination therapy is developed comprising a novel ciprofloxacin derivative‐loaded PEGylated polymeric nanoparticles (CIP2b‐NPs) and paclitaxel (PTX) against human type‐II endometrial cancer (Hec50co with loss of function p53). Cytotoxicity studies reveal strong synergy between CIP2b and PTX against Hec50co, and this is associated with a significant reduction in the IC50 of PTX and increased G2/M arrest. Upon formulation of CIP2b into PEGylated polymeric nanoparticles, tumor accumulation of CIP2b is significantly improved compared to its soluble counterpart; thus, enhancing the overall antitumor activity of CIP2b when co‐administered with PTX. In addition, the co‐delivery of CIP2b‐NPs with paclitaxel results in a significant reduction in tumor progression. Histological examination of vital organs and blood chemistry was normal, confirming the absence of any apparent off‐target toxicity. Thus, in a mouse model of human endometrial cancer, the combination of CIP2b‐NPs and PTX exhibits superior therapeutic activity in targeting human type‐II endometrial cancer. CIP2b synergizes with paclitaxel to combat resistant endometrial cancer. CIP2b‐loaded nanoparticles (CIP2b NPs) show several‐fold higher intracellular uptake in endometrial cancer cells in vitro, and higher intra‐tumoral levels of CIP2b in vivo, compared to unencapsulated CIP2b. CIP2b NPs and paclitaxel significantly slow endometrial cancer tumor growth in mice, compared to paclitaxel with drug‐free nanoparticles, or paclitaxel with free unencapsulated CIP2b.