Anti-CD133-grafted single-walled carbon nanotubes as doxorubicin carrier

Elham Momeni; Rahime Eshaghi Malekshah; Ali Khaleghian; Fahimeh Shamsi; Mohsen Nabi-Afjadi

doi:10.1186/s12575-025-00306-0

Anti-CD133-grafted single-walled carbon nanotubes as doxorubicin carrier

Biol Proced Online. 2025 Nov 17;27(1):44. doi: 10.1186/s12575-025-00306-0.

Authors

Elham Momeni¹, Rahime Eshaghi Malekshah², Ali Khaleghian^{3

4}, Fahimeh Shamsi⁵, Mohsen Nabi-Afjadi⁶

Affiliations

¹ Department of Biochemistry, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
² Medical Biomaterial Research Center (MBRC), Tehran University of Medical Sciences, Tehran, Iran.
³ Department of Biochemistry, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran. khaleghian@semums.ac.ir.
⁴ Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran. khaleghian@semums.ac.ir.
⁵ Department of Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran. fahimeh.shamsi@ymail.com.
⁶ Department of Biochemistry, Faculty of biological sciences, Tarbiat Modares University, Tehran, Iran.

Abstract

Background: Advances in nanomedicine have spurred interest in antibody-conjugated carbon nanotubes for targeted cancer therapy. CD133, a marker enriched in chemoresistant cancer stem cells, presents a strategic target for precision drug delivery. This study explores functionalized single-walled carbon nanotubes (SWCNTs) as dual-action platforms for enhanced doxorubicin (DXR) delivery and CD133-specific targeting.

Methods: Two nano formulations-SWCNT-Ab/DXR (antibody-functionalized) and SWCNT-PEG-Ab/DXR (pegylated antibody-functionalized)-were engineered to encapsulate DXR. Release profiles, cytotoxicity, and apoptosis were assessed in CD133⁺ HT-29 colorectal cancer cells and CD133^- CHO control cells. Computational modeling included DFT-D structural optimization, Monte Carlo adsorption simulations for DXR binding analysis, and molecular docking to evaluate carrier-receptor interactions.

Results: PEGylation markedly enhanced colloidal stability and drug-loading capacity, with SWCNT-PEG-Ab/DXR achieving 92% DXR encapsulation vs. 78% for non-PEGylated counterparts. In vitro, the PEGylated system showed amplified cytotoxicity (IC50: 2.1 µM vs. 3.8 µM for SWCNT-Ab/DXR) and 1.7-fold higher apoptosis induction in HT-29 cells. Computational data aligned with experimental findings: DXR adsorption energy was strongest on PEG-NH₂-modified SWCNTs (- 32.6 kcal/mol) versus carboxylated variants (- 24.8 kcal/mol), confirming PEG's role in stabilizing drug-carrier interactions.

Conclusions: By integrating PEG-mediated stealth properties, charge-modified surfaces, and antibody targeting, SWCNT-PEG-Ab/DXR emerges as a multifunctional nanoplatform with enhanced tumor selectivity and therapeutic payload delivery. This dual experimental-computational approach underscores the potential of rationally engineered nanotubes to overcome limitations in conventional chemotherapy.

Keywords: CD133Ab; Cytotoxicity; Doxorubicin; Monte carlo locator module; Polyethylenglycol; SWCNTs.