Magnetic and Non-Magnetic Halloysite Nanotubes Functionalized with Folic Acid for the Targeted Delivery of [Pd(dipic)Cl].H2O: Cytotoxicity and Apoptosis Induction in Colon Cancer Cells.

INTRODUCTION

Cisplatin and its analogs are commonly used in cancer therapy, but the lack of differentiation between healthy and cancer cells often leads to severe side effects.

METHODS

To address this problem, magnetic and non-magnetic Halloysite Nanotubes (HNTs) modified with folic acid (Fe-HNTs-FA and HNTs-FA) were developed, and the [Pd(dipic)Cl].H2O complex was encapsulated inside them. Cell viability was measured using the MTT assay. Real-time PCR was used to evaluate apoptosisrelated genes and the drug resistance marker. Oxidative stress in erythrocytes was assessed to confirm biocompatibility.

RESULTS

The Encapsulation Efficiency (EE%) of [Pd(dipic)Cl].H2O in the pores of Fe-HNTs-FA was found to be 29%. Fe-HNTs-FA-[Pd(dipic)Cl].H2O reduced cell viability to below 50%. HNTs-FA-[Pd(dipic)Cl].H2O showed cytotoxic effects at higher concentrations. The [Pd(dipic)Cl].H2O complex and cisplatin did not effectively inhibit the growth of HCT116 colon cancer cells. Real-time PCR analysis showed that the presence of Fe3O4 Nanoparticles (NPs) on Fe-HNTs-FA-[Pd(dipic)Cl].H2O increased the Bak1/Bclx ratio by 14.4-fold compared to the control group. Other compounds only increased the expression of caspase-3. The expression level of AKT1 was 1.39 for the free complex, and 0.076 and 0.078 for Fe-HNTs-FA-[Pd(dipic)Cl].H2O and HNTs-FA- [Pd(dipic)Cl].H2O, respectively. Furthermore, the modified HNTs did not induce oxidative stress in erythrocytes.

DISCUSSION: This targeted delivery induced apoptosis via extrinsic and intrinsic pathways, increased caspase-3 activation, and abolished drug resistance by downregulating AKT1 expression. The Fe-HNTs-FA- [Pd(dipic)Cl].H2O showed the potential to be a safer and more effective alternative to cisplatin without causing oxidative damage to erythrocytes.

CONCLUSION

The positive properties of Fe-HNTs-FA-[Pd(dipic)Cl].H2O make it a promising candidate for targeted therapy of colon cancer.