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

Background/Objectives: 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. Methods: In this study, halloysite (Hall) was functionalized with green-synthesized 2 wt% zinc oxide (GZn) and silver (GAg) nanoparticles (NPs) using Tribulus terrestris extract (25 mM) to enhance cisplatin (Cp) and carboplatin (Cbpt) delivery for targeted cervical cancer therapy. Results: 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. Conclusions: 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.