Publication: Development, characterization and evaluation of 5-fluorouracil loaded gold nanoparticles conjugated with cd133 antibody targeting positive-survivin colorectal cancer stem cells
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Date
2025-11
Authors
Zahid, Manali Haniti Mohd.
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Abstract
Ranked second in cancer-related mortality, colorectal cancer (CRC) presents significant challenges in treatment, such as resistance to chemotherapy, recurrence, and adverse toxic effects. Conventional chemotherapeutic strategies that target actively dividing cells are unable to eradicate cancer stem cells (CSCs) due to the slow-cycling nature of CSCs, which results in disease recurrence and metastasis. The use of nanotechnology in drug delivery to specifically target CSCs presents a highly promising strategy to improve treatment effectiveness while reducing adverse effects. This study focused on the synthesis of gold nanoparticles (AuNPs) using the Turkevich method, subsequently modified with polyethylene glycol, conjugated with anti-CD133 monoclonal antibody (mAb), and loaded with 5-fluorouracil (5-FU) to develop a targeted nanocarrier system. The synthesized nanoparticles were characterized by X-ray diffraction (XRD), UV-vis spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). The approach of functionalization with anti-CD133 mAb facilitated the specific intracellular intake of AuNPs in HCT116 CRC cells, as demonstrated by fluorescence microscopy, which indicated their localization within the nuclear region of the cells. Cytotoxicity studies demonstrated that 5FU-AuNPs-CD133 significantly reduced cell viability (p < 0.0001) and hindered HCT116-derived colonospheres relative to non-targeted AuNP formulations, highlighting a strong inhibition of self-renewal activity in CRCSCs. Western blot examination revealed a decrease in survivin, an anti-apoptotic protein associated with the survival of cancer cells, in the treated colonospheres. These findings highlight the potential of CD133-targeted AuNPs as an effective nanocarrier system for colorectal cancer therapy, particularly through the selective targeting of cancer stem cells and enhancing the delivery of 5-FU. Future studies should focus on elucidating the fundamental mechanisms involved and enhancing formulation strategies for the improvement of therapeutic window and successful clinical implementation.