Purpose: This study presents a novel and sustainable approach to cancer therapy by combining halloysite nanotubes (HNTs), green‐synthesized copper oxide (CuO) nanoparticles, and curcumin (CUR). We demonstrate that the green synthesis of CuO nanoparticles, when combined with CUR and incorporated into HNTs, enhances the delivery and anticancer effects of CUR. This innovative complex could address some of the critical limitations of current anticancer therapies such as poor pharmacokinetics and drug resistance by providing a controlled release mechanism and leveraging the benefits of combination therapy. Methods: We synthesized CuO using green synthesis with lemon peel extract and used this synthesized CuO to formulate a complex with HNT and CUR (CHC). Comprehensive characterization was conducted using UV‐visible spectroscopy, scanning electron microscopy‐energy‐dispersive X‐ray spectroscopy (SEM–EDX), X‐ray diffraction (XRD), thermogravimetric analysis (TGA), and Fourier‐transform infrared spectroscopy (FTIR). We also examined the release kinetics of the formulation. In vitro experiments were performed to evaluate the anticancer effects of the complex on HMVII, HepG2, and MCF‐7 cancer cell lines. In addition, an in silico docking assessment and a 10 ns molecular dynamics simulation were conducted to determine the interaction between CUR and HNTs. Results: The characterization of HNTs loaded with CUR showed a drug loading efficiency of 3%–5% and an encapsulation efficiency of 15%–20%. Drug release kinetics were best described by the Hixson–Crowell model for CHC‐50 and CHC‐20, with R ² = 0.9897 and R ² = 0.9900 respectively. CHC‐10 fit the Higuchi model ( R ² = 0.8838), while free CUR fit the Korsmeyer–Peppas model ( R ² = 0.9212). The formulations demonstrated significant anticancer effects across all tested cell lines, with CHC‐10 showing the lowest IC ₅₀ value of 10.43 μg/mL. The CHC formulations exhibited enhanced delivery and maintained significant anticancer activity compared to CUR across HepG2, MCF‐7, and HMVII cell lines, with lower IC50 values after UV exposure. Molecular docking analysis revealed a CUR–HNT binding score of −3.803, with the complex remaining stable over a 10 ns simulation. Conclusion: This study demonstrates the successful integration of green‐synthesized CuO nanoparticles with CUR‐loaded HNTs as a novel approach to cancer therapy. The enhanced anticancer effects of the CHC‐10 formulation, coupled with the complex’s stability, suggest significant potential for improving cancer treatment outcomes. This innovative, sustainable approach addresses key limitations of current therapies, potentially offering more effective and patient‐friendly treatments with reduced side effects. Our findings pave the way for further development of targeted, environmentally conscious cancer therapies.

Cisplatin is a common and highly effective chemotherapeutic agent whose nephrotoxic side effect is well-characterized. Sodium thiosulfate (STS), an FDA-approved hydrogen sulfide (H₂S) donor drug, is emerging as a chemoprotective agent against cisplatin-induced nephrotoxicity (CIN). In this study, we investigated the chemoprotective mechanism of STS in a rat model of CIN. Twenty-five male Sprague Dawley rats were randomly assigned to the following groups: HC: Healthy control (received 10 mL/kg/day of 0.9% saline intraperitoneally (ip), [n = 5]), CIN: Cisplatin (received single dose of 7 mg/kg cisplatin ip [n = 5]); CIN + PAG: Cisplatin and daily ip administration of 40 mg/kg of the H₂S inhibitor, DL-propargylglycine (PAG) for 28 days (n = 5); CIN + PAG + STS: Cisplatin and daily PAG and STS (150 µM) ip injection for 28 days; CIN + STS: Cisplatin and daily STS ip administration for 28 days (n = 5). Rats in each group were kept in metabolic cages for 24 h on day 0, 14 and 29 after cisplatin administration for urine collection. Rats were then euthanized, and kidney and blood samples were collected for analysis. Histologically, CIN was characterized by glomerular and tubular injury and significant macrophage influx and tubular apoptosis, as well as markedly increased levels of plasma and renal IL-1β, IL-6 and TNF-α and impaired renal antioxidant status compared to HC rats (p < 0.001). These pathological changes were exacerbated in CIN + PAG rats and were strongly reduced in CIN + PAG + STS rats relative to CIN + PAG rats (p < 0.01), while superior renal protection was observed in CIN + STS rats. Functionally, CIN was evidenced by markedly increased levels of serum creatinine and BUN, and significantly decreased urine creatinine, renal creatinine clearance, as well as electrolyte imbalance and urinary concentrating defect in comparison with HC (p < 0.01). These functional changes worsened significantly in CIN + PAG rats (p < 0.05) but improved in CIN + PAG + STS rats, with further improvement in CIN + STS rats to levels comparable to HC rats. Mechanistically, STS increased renal and plasma levels of H₂S, arginine, cAMP, nitric oxide (NO) and cGMP as well as SIRT3 and PGC-1α. We have shown for the first time that STS provides chemoprotection against CIN by activating renal arginine/cAMP and NO/cGMP signaling pathways and their downstream mechanisms through increased renal H₂S production.

G protein-coupled receptors (GPCRs) mediate a variety of signaling pathways and represent the most common class of pharmaceutical target. While advances in structural biochemistry have provided deep functional insights into key receptors, many of the 800+ human GPCRs remain understudied. We introduce a versatile “deep receptor scanning” platform that can be used to experimentally characterize 766 human GPCRs and 174 known GPCR splice variants in parallel. We use this platform to quantitatively characterize the relative abundance of canonical and alternative receptor transcripts, their translational efficiency, and the plasma membrane expression of each receptor in the context of a recombinant pool of HEK293T cells expressing individual GPCRs. We then employ machine learning to identify specific structural features that are strongly associated with variations in GPCR expression. Our results show that many highly-expressed receptors exhibit systematic differences in hydrophobicity and secondary structure. This experimental platform and informatic approach are compatible with a variety of assays and can be used to efficiently explore the biochemical and pharmacological properties of the GPCRome.

Levodopa is routinely co-administered with carbidopa in the management of Parkinson’s disease. Although the aforementioned combination therapy is effective, there may be fluctuating plasma levels of levodopa after oral administration. We formulated and evaluated the kinetic characteristics of the chitosan-pectin-based multiparticulate matrix of levodopa and carbidopa. Pectin was extracted from the cocoa husk, and the chitosan-pectin-based matrix was prepared by wet granulation. Formulations were evaluated for drug-excipient compatibility, drug content, precompression properties and in vitro release. For pharmacokinetic evaluation, rats were put into groups and administered either chitosan-pectin based matrix of levodopa/carbidopa, Sinemet® CR or levodopa/carbidopa immediate release powder. Rats were administered the different formulations of levodopa/carbidopa (20/5 mg/kg) per os every 12 hours. The pharmacokinetic parameters of levodopa were estimated for the various treatment groups. The percentage content of levodopa and carbidopa in the various formulations was within the acceptance criteria. The AUC0-24 for levodopa/carbidopa multiparticulate matrix (Formulation 3: 484.98 ± 18.70 µg.hr/mL); Formulation 4: 535.60 ± 33.04 µg.hr/mL), and Cmax (Formulation 3: 36.28 ± 1.52 μg/mL; Formulation 4: 34.80 ± 2.19 μg/mL) were higher than Sinemet® CR (AUC0-24 262.84 ± 16.73 µg.hr/mL and Cmax 30.62 ± 3.37 μg/mL). The t1/2 of the new formulation was longer compared to Sinemet® CR.