Tribulus terrestris-Mediated ZnO/Ag-Halloysite Nanohybrids for Targeted Cisplatin and Carboplatin Delivery in Cervical Cancer Treatment

<b>Background/Objectives:</b> Cervical cancer remains a major health challenge, especially in low-resource regions with limited diagnostic and advanced treatment options. Nanotechnology-based strategies offer promising alternatives to conventional chemotherapy by reducing systemic toxicity and enabling site-specific delivery. <b>Methods:</b> In this study, halloysite (Hall) was functionalized with green-synthesized 2 wt% zinc oxide (GZn) and silver (GAg) nanoparticles (NPs) using <i>Tribulus terrestris</i> extract (25 mM) to enhance cisplatin (Cp) and carboplatin (Cbpt) delivery for targeted cervical cancer therapy. <b>Results:</b> Structural and morphological analyses confirmed the successful integration of GZn and GAg NPs into the Hall without compromising its tubular integrity. Cp or Cbpt adsorption studies with varying times (0.15-12 h), as well as drug/Hall ratios (10-50) and pH levels (5; 6.6; 7.4; 9.0; and 10.5), revealed greater Cp adsorption than Cbpt, attributed to its higher reactivity and affinity toward the Hall surface. pH-responsive release studies biphasic drug release for non-PEGYlated formulations, with Cp (14% with 2 h) and Cbpt (10% with 0.5 h), whereas PEGYlated systems exhibited sustained release under acidic tumor-like conditions, achieving 14% in 72 h for Cp and 4.5% in 72 h for Cbpt. Release kinetics followed either Fickian or non-Fickian diffusion depending on pH and drug type, with the Korsmeyer-Peppas model offering a strong fit (R² > 0.85). In vitro assays revealed that Cbpt/GZn-Hall/PEG, Cp/GZn-Hall/PEG, and Cbpt/GAg-Hall/PEG induced dose-dependent cytotoxicity against HeLa while sparing HFF-1 fibroblasts. <b>Conclusions:</b> These findings indicate that green-synthesized nanohybrids are promising carriers for targeted Cp and Cbpt delivery, warranting further in vivo evaluation for cervical cancer therapy.