Silvija Šafranko

Citrus fruits processing results in the generation of huge amounts of citrus by-products, mainly peels, pulp, membranes, and seeds. Although they represent a major concern from both economical and environmental aspects, it is very important to emphasize that these by-products contain a rich source of value-added bioactive compounds with a wide spectrum of applications in the food, cosmetic, and pharmaceutical industries. The primary aim of this review is to highlight the great potential of isolated phytochemicals and extracts of individual citrus by-products with bioactive properties (e.g., antitumor, antimicrobial, antiviral, antidiabetic, antioxidant, and other beneficial activities with health-promoting abilities) and their potential in pharmaceutical, biomedical, and biological applications. This review on citrus by-products contains the following parts: structural and chemical characteristics; the utilization of citrus by-products; bioactivities of the present waxes and carotenoids, essential oils, pectins, and phenolic compounds; and citrus by-product formulations with enhanced biocactivities. A summary of the recent developments in applying citrus by-products for the treatment of different diseases and the protection of human health is also provided, emphasizing innovative methods for bioaccessibility enhancements (e.g., extract/component encapsulation, synthesis of biomass-derived nanoparticles, nanocarriers, or biofilm preparation). Based on the representative phytochemical groups, an evaluation of the recent studies of the past six years (from 2018 to 2023) reporting specific biological and health-promoting activities of citrus-based by-products is also provided. Finally, this review discusses advanced and modern approaches in pharmaceutical/biological formulations and drug delivery (e.g., carbon precursors for the preparation of nanoparticles with promising antimicrobial activity, the production of fluorescent nanoparticles with potential application as antitumor agents, and in cellular imaging). The recent studies implementing nanotechnology in food science and biotechnology could bring about new insights into providing innovative solutions for new pharmaceutical and medical discoveries.

This work reports the preparation of amino acid-functionalized CQDs from citric acid by facile hydrothermal synthesis. The prepared N-doped CQDs exhibited excellent optical, physical, and chemical properties, and the differences were observed among the six different amino acids used as nitrogen dopants (Leu, Trp, Lys, Arg, Ala, His). Compared to the blank sample (without the addition of amino acids), N-doped CQDs have shown significantly higher quantum yield, also demonstrating the potential in metal ion sensing. The highest quantum yield of 36.45%, with a peak excitation/emission of 340/406 nm, was achieved using citric acid and amino acid Leu (CQD@Leu), treated at temperature of 180 °C during 9 h. The prepared samples were investigated toward metal ion selectivity (Ca²⁺, Cu²⁺, Fe³⁺, K⁺, Hg²⁺, Mg²⁺, Al³⁺, Mn²⁺, and Na⁺), and the CQD@Leu showed a selective and sensitive response upon the addition of Fe³⁺ ions. Therefore, CQD@Leu was selected for further investigation in Fe³⁺ detection in the model system and real well water samples. A developed model was described by a logistic function with a good coefficient of determination of R² = 0.9982, while the linear range was determined in the concentration range from 0.3 mol dm⁻³ to 30 mol dm⁻³, with a determined limit of detection of LOD = 1.77 ± 0.01 mol dm⁻³ and limit of quantification of LOQ = 5.89 ± 0.04 mol dm⁻³. Furthermore, the results of the in vitro cytotoxicity test (MTT) with normal and tumor cell lines (MRC-5, HeLa, NCI-H358, and CaCo-2) clearly demonstrate the excellent biocompatibility of CQD@Leu.

Carbon quantum dots (CQDs) have recently emerged as innovative theranostic nanomaterials, enabling fast and effective diagnosis and treatment. In this study, a facile hydrothermal approach for N-doped biomass-derived CQDs preparation from Citrus clementina peel and amino acids glycine (Gly) and arginine (Arg) has been presented. The gradual increase in the N-dopant (amino acids) nitrogen content increased the quantum yield of synthesized CQDs. The prepared CQDs exhibited good biocompatibility, stability in aqueous, and high ionic strength media, similar optical properties, while differences were observed regarding the structural and chemical diversity, and biological and antioxidant activity. The antiproliferative effect of CQD@Gly against pancreatic cancer cell lines (CFPAC-1) was observed. At the same time, CQD@Arg has demonstrated the highest quantum yield and antioxidant activity by DPPH scavenging radical method of 81.39 ± 0.39% and has been further used for the ion sensing and cellular imaging of cancer cells. The obtained results have demonstrated selective response toward Fe³⁺ detection, with linear response ranging from 7.0 µmol dm⁻³ to 50.0 µmol dm⁻³ with R² = 0.9931 and limit of detection (LOD) of 4.57 ± 0.27 µmol dm⁻³. This research could be a good example of sustainable biomass waste utilization with potential for biomedical analysis and ion sensing applications.

The search for an efficient drug or inhibitor in the formation process of kidney stones has been a promising research topic towards reducing the risks of the formation of disease. However, several challenges have been faced in investigating the most common constituents of kidney stones, calcium oxalate and its hydrate forms (COM, COD and COT). This study focuses on the preparation and structural characterization (TG, XRD, FTIR, SEM) of calcium oxalate hydrates in the presence of gallic acid (GA) and by varying operating parameters such as temperature (25 °C, 36.5 °C and 48 °C), pH (5.6, 6.5 and 7.5) and amount of added GA (ranging from 100 mg to 1000 mg). Response surface methodology was applied in order to evaluate the effects of operating parameters in the formation of COM and COD, and for the process optimization towards maximizing their content in samples. The results indicated that GA inhibited the formation of COM (0–100%) and promoted the formation of COD (0 ≤ 99%), while a medium pH and the amount of added GA showed a significant effect in the process of COD formation. In order to investigate the interactions established in the formation process and the possible adsorption between GA and the formed crystals, electrochemical measurements were performed.

The fluorescent carbon quantum dots (CQDs) represent an emerging subset of carbonaceous nanomaterials, recently becoming a powerful tool for biosensing, bioimaging, and drug and gene delivery. In general, carbon dots are defined as zero-dimensional (0D), spherical-like nanoparticles with <10 nm in size. Their unique chemical, optical, and electronic properties make CQDs versatile materials for a wide spectrum of applications, mainly for the sensing and biomedical purposes. Due to their good biocompatibility, water solubility, and relatively facile modification, these novel materials have attracted tremendous interest in recent years, which is especially important for nanotechnology and nanoscience expertise. The preparation of the biomass-derived CQDs has attracted growing interest recently due to their low-cost, renewable, and green biomass resources, presenting also the variability of possible modification for the enhancement of CQDs’ properties. This review is primarily focused on the recent developments in carbon dots and their application in the sensing of different chemical species within the last five years. Furthermore, special emphasis has been made regarding the green approaches for obtaining CQDs and nanomaterial characterization toward better understanding the mechanisms of photoluminescent behavior and sensing performance. In addition, some of the challenges and future outlooks in CQDs research have been briefly outlined.

In this study, an efficient utilization and valorization of mandarin peel (Citrus unshiu Marc. var. Kuno) was investigated using innovative and green extraction techniques. The first step of this study included the extraction and analysis of the volatile compounds by performing a supercritical CO₂ (SC-CO₂) extraction under different operating pressure conditions (100 and 300 bar). The analysis of volatile compounds of the obtained extracts was conducted by gas chromatography-mass spectrometry (GC-MS), and limonene was found to be the dominant volatile component (13.16% at 100 bar; 30.65% at 300 bar). After SC-CO₂ treatment, the exhausted citrus peel waste enriched with bioactive compounds was subjected to subcritical water extraction (SWE) in a wide temperature range (130–220 °C) using different solvent-solid ratio (10–30 mL/g) in time periods from 5 to 15 min, in order to obtain bioflavonoids. Identification and quantification of present bioflavonoids was conducted by high-performance liquid chromatography with a with a diode array detector (HPLC), and hesperidin (0.16–15.07 mg/g) was determined as the most abundant flavanon in mandarin peel with other polyphenolic compounds that were possible by-products of thermal degradation. At higher temperatures, the presence of 5-hydroxymethylfurfural (5-HMF) and chlorogenic acid were detected. Antiradical activity and total phenolic content in the extracts were determined using spectrophotometric methods, while the process optimization was performed by response surface methodology (RSM).

Spontaneous precipitation of calcium oxalate monohydrate (COM) in additive-free systems with nearly the same initial supersaturation has been investigated. The influence of thermodynamic parameters such as: temperature (t = 25, 36.5 and...