Contamination of trace, non-essential/heavy metals in nutraceuticals/dietary supplements: A chemometric modelling approach and evaluation of human health risk upon dietary exposure.

Across the world, nutraceuticals/dietary supplements are commonly consumed without medical supervision, and believing these products are harmless to health. However, these products may contain trace (TMs) and non-essential/heavy metals (nHMs) as contaminants at levels higher than the recommended daily allowance (RDA), which can be hazardous to human health. Consequently, it is crucial to assess the levels of these metals to ensure the safety of these products. This study aimed to analyze the concentration of TMs (Mn, Cu and Zn) and nHMs (Al, Cr, Ni, Cd and Pb) in nutraceuticals/dietary supplements. Metal analysis was conducted using inductively coupled plasma-optical emission spectrometry (ICP-OES). Multivariate and bivariate analysis including principle component analysis (PCA), hierarchical cluster analysis (HCA) and Pearson correlation coefficient (PCC) were applied to understand inter-metal association and sources of these metals. Concentration ranges for TMs were found as, Mn (0.2-4.3 mg/kg), Cu (0.11-2.54 mg/kg), and Zn (0.1-22.66 mg/kg) while the nHMs concentration ranges were: Al (0.046-3.336 mg/kg), Cr (0.11-1.63 mg/kg), Ni (0.18-0.72 mg/kg), Cd (0.04-0.92 mg/kg), and Pb (0.18-1.08 mg/kg). The levels of tolerable dietary intake (TDI) for Cr and Ni, and the provisional tolerable monthly intake (PTMI) limit for Cd, exceeded the values set by the World Health Organization (WHO) and the European Food Safety Authority (EFSA). The estimation of the target hazard quotient (THQ <1), hazard index (HI < 1) and cumulative cancer risk (CCR <1 ✕ 10-3) indicated no significant non-carcinogenic and carcinogenic health risks associated with consuming these products. Therefore, the primary recommendation from this study is to use the nutraceuticals/dietary supplements should be under the supervision of dietitian.

Appraisal of potentially toxic metals contamination in protein supplements for muscle growth: A chemometric approach and associated human health risks.

BACKGROUND: The use of protein supplements by athletes has risen due to their effectiveness in meeting dietary needs. However, there is a growing concern about the presence of potentially toxic metals (PTMs. Al, Cr, Mn, Ni, Cu, Zn, Cd, and Pb) in these supplements. Consequently, it is crucial to evaluate the levels of these PTMs to ensure the safety of the supplements. METHODS: The objective of the current study was to assess the PTMs concentrations in protein supplements and examine any possible health hazards. Twenty-five samples of protein supplements were purchased from different pharmacies to screen them for metals. Inductively coupled plasma-optical emission spectrometry (ICP-OES) was utilized to analyze metal content. Additionally, chemometric methods such as Pearson's correlation coefficient (PCC), principal component analysis (PCA), and hierarchical cluster analysis (HCA) were employed to identify possible sources of PTMs contamination in protein supplements. RESULTS: Concentration ranges for PTMs were found as, Al (0.03-3.05 mg/kg), Cr (0.11-0.89 mg/kg), Mn (1.13-8.40 mg/kg), Ni (0.06-0.71 mg/kg), Cu (1.05-5.51 mg/kg), Zn (2.14-27.10 mg/kg), Cd (0.01-0.78 mg/kg), and Pb (0.06-0.57 mg/kg). The weekly intake of Cd exceeded the level of tolerable weekly intake (TWI) set by the European Food Safety Authority (EFSA). CONCLUSION: Athletes, bodybuilders, fitness enthusiasts, dieters, young adults and adolescents, and health-conscious individuals should be conscious of Cd concentration as it does not compliance the TWI set by EFSA. Target hazard quotient (THQ < 1), hazard index (HI < 1), margin of exposure (MOE ≥ 1), percentile permitted daily exposure (% PDE < 100), and cumulative cancer risk (CCR < 1 × 10-3) analyses revealed that there are no appreciable non-carcinogenic and carcinogenic health risks associated with the use of these products.

Development of immunoliposomes containing cytotoxic gold payloads against HER2-positive breast cancers.

Overexpression of the human epidermal growth factor receptor 2 (HER2) is found in 20-30% of breast cancer tumors (HER2-positive breast cancers) and is associated with more aggressive onset of disease, higher recurrence rate and increased mortality. Monoclonal antibodies (mAb) like trastuzumab and pertuzumab in combination with chemotherapeutics, and trastuzumab-based antibody drug conjugates (ADCs) are used in the clinic to treat these cancers. An alternative targeted strategy (not yet in clinical use) is the encapsulation of chemotherapeutic drugs in immunoliposomes. Such systems may not only facilitate targeted delivery to the tumor and improve intracellular penetration, but also override some of the resistance developed by tumors in response to cytotoxic loads. As a supplement to classical chemotherapeutics (based on organic compounds and conventional platinum-based derivatives), gold compounds are emerging as potential anticancer agents due to their high cytotoxicity and capacity for immunogenic cell death. Here, we describe the development of immunoliposomes functionalized with trastuzumab and pertuzumab; containing simple gold(i) neutral compounds ([AuCl(PR3)] (PR3 = PPh3 (1), PEt3 (2))) generated by the thin-film method to afford Lipo-1-Lipo-2. Trastuzumab and pertuzumab were engrafted onto these liposomes to generate gold-based immunoliposomes (Immunolipo-Tras-1, Immunolipo-Tras-2, Immunolipo-Per-1, Immunolipo-Per-2). We have characterized all liposomal formulations and demonstrated that the immunoliposomes (190 nm) are stable, have high binding affinity for HER2, and display selective cytotoxicity towards HER2-positive breast cancer cell lines. Trastuzumab-based immunoliposomes of a smaller size (100 nm) - encapsulating [AuCl(PEt3)] (2) - have been generated by an extrusion homogenization method. These optimized immunoliposomes (Opt-Immunolipo-Tras-2) have a trastuzumab engraftment efficiency, encapsulation efficiency for 2, and affinity for HER-2 similar to the immunoliposomes obtained by sonication (Immunolipo-Tras-2). While the amount of Au encapsulated is slightly lower, they display almost identical cytotoxicity and selectivity profiles. Moreover, the fluorescently-labeled phosphane drug [AuCl(PPh2-BODIPY)] (3) was encapsulated in both larger (Immunolipo-Tras-3) and smaller (Opt-Immunolipo-Tras-3) immunoliposomes and used to visualize the intracellular localization of the payload. Fluorescent imaging studies found that Opt-Immunolipo-Tras-3 accumulates in the cells more than 3 and that the unencapsulated payload accumulates primarily in lysosomes, while targeted liposomal 3 localizes in mitochondria and ER, hinting at different possibilities for modes of action.