Background: Irinotecan is a promising antitumor agent approved by FDA for intravenous use in colon cancer treatment either alone or in combination. It is a topoisomerase inhibitor and by blocking the topoisomerase-I enzyme, it causes DNA damage and results in cell death. However, it lacks selectivity and specificity for tumor cells, resulting in systemic toxicity. Thus, it is essential to reduce its side effects and improve therapeutic efficacy.
Objective: The study aimed to improve the therapeutic efficacy and minimize the toxic effects of irinotecan by developing a fullerene functionalized biotin drug delivery system and adsorbing irinotecan on the surface of the functionalized fullerene-biotin complex.
Methods: Fullerene (C) has been observed as a potential drug delivery agent and the aminefunctionalized C-NH was synthesized by functionalizing ethylenediamine on the surface of C. The PEI functionalized C was further synthesized by polymerization of aziridine on the surface of C- NH2. Biotin was attached by an amide linkage to C-PEI and the anti-colon cancer drug irinotecan (IRI) was encapsulated (C-PEI-Biotin/IRI). The C-PEI-Biotin/IRI was characterized and evaluated for in vivo anti-colon cancer activity in rats and the results were compared with the parent drug irinotecan.
Results: The results showed that C-PEI-Biotin/IRI conjugate had a controlled release profile according to in vitro HPLC studies. Moreover in vivo anti-tumor studies suggested that the conjugate proved to be less toxic to vital organs and had high efficacy towards tumor cells. Statistical studies confirmed less tumor index and tumor burden in the case of conjugate when compared to irinotecan.
Conclusion: It is hypothesized that the conjugate (C-PEI-Biotin/IRI) could cross the cell membrane easily through overexpressed biotin receptors on the cell surface of colon cancer cells and showed better efficacy and less toxicity in comparison to IRI in the colon cancer rat model.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/1567201819666220516153010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Background And Aim: The high rate of tumor growth results in an increased need for amino acids. As solute carriers (SLC) transporters are capable of transporting different amino acids, cancer may develop as a result of these transporters' over-expression due to their complex formation with other biological molecules. Therefore, this review investigated the role of SLC transporters in the progression of cancer.
View Article and Find Full Text PDFA pectic polysaccharide from Murray alleviates dextran sulfate sodium-induced colitis in mice.
Curr Res Food Sci
December 2024
Department of Immunology, College of Basic Medical Sciences, Jilin University, 126 Xin min Street, Changchun, 130021, China.
Inflammatory bowel disorders (IBD) can lead to severe complications like perforation, bleeding, and colon cancer, posing life-threatening risks. Murray ( Murr.), rich in polysaccharides, has been utilized in traditional diets for thousands of years.
View Article and Find Full Text PDFTargeted inhibition of Gus-expressing to promote intestinal stem cell and epithelial renovation contributes to the relief of irinotecan chemotoxicity by dehydrodiisoeugenol.
Acta Pharm Sin B
December 2024
The MOE Key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Irinotecan (CPT11) chemotherapy-induced diarrhea affects a substantial cancer population due to -glucuronidase (Gus) converting 10--glucuronyl-7-ethyl-10-hydroxycamptothecin (SN38G) to toxic 7-ethyl-10-hydroxycamptothecin (SN38). Existing interventions primarily address inflammation and Gus enzyme inhibition, neglecting epithelial repair and Gus-expressing bacteria. Herein, we discovered that dehydrodiisoeugenol (DDIE), isolated from nutmeg, alleviates CPT11-induced intestinal mucositis alongside a synergistic antitumor effect with CPT11 by improving weight loss, colon shortening, epithelial barrier dysfunction, goblet cells and intestinal stem cells (ISCs) loss, and wound-healing.
View Article and Find Full Text PDFIntegrated analysis of non‑coding RNAs (HOTAIR and miR‑130a) and their cross‑talk with TGF‑β1, SIRT1 and E‑cadherin as potential biomarkers in colorectal cancer.
Oncol Lett
March 2025
Department of Biochemistry, Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt.
Molecular changes have a substantial impact on the onset of colorectal cancer (CRC). Complexes of HOTAIR and miRNAs disrupt several cellular functions during carcinogenesis, primarily by disrupting several carcinogenic signaling pathways. In the present study, the relationships between the serum levels of transforming growth factor-β1 (TGF-β1), sirtuin-1 (SIRT1) and E-cadherin and those of HOX transcript antisense intergenic RNA (HOTAIR) and microRNA-130a (miR-130a) in individuals with CRC were analyzed, including their correlations and diagnostic potential.
View Article and Find Full Text PDFDesign and validation of a simulation-based training module for ileo-transverse intracorporeal anastomosis.
Surg Endosc
January 2025
Colorectal Surgery Unit, Department of Digestive Surgery, Pontificia Universidad Católica de Chile, Uc-Christus Health Network, Santiago, Chile.
Background: The benefits of the totally laparoscopic right hemicolectomy have been established, but its adoption has been limited by the challenges of intracorporeal suturing. While simulation is effective for training advanced surgical skills, no dedicated simulation-based course exists for intracorporeal ileo-transverse anastomosis (ICA). This study aimed to develop and validate a simulation module for training in ICA.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!