Ciprofloxacin Derivative‐Loaded Nanoparticles Synergize with Paclitaxel Against Type II Human Endometrial Cancer
Youssef W. Naguib, Suhaila O. Alhaj‐Suliman, Emad I. Wafa, Sanjib Saha, Kareem Ebeid, Hamada Hashem, Somaya A. Abdel‐Rahman, Gamal El‐Din A. Abuo‐Rahma, Sean M. Geary, Aliasger K. Salem
Abstract
Abstract 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 IC 50 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.