Green Nanotechnology Through Papain Nanoparticles: Preclinical in vitro and in vivo Evaluation of Imaging Triple-Negative Breast Tumors.

Background: Recent advancements in nanomedicine and nanotechnology have expanded the scope of multifunctional nanostructures, offering innovative solutions for targeted drug delivery and diagnostic agents in oncology and nuclear medicine. Nanoparticles, particularly those derived from natural sources, hold immense potential in overcoming biological barriers to enhance therapeutic efficacy and diagnostic accuracy. Papain, a natural plant protease derived from Carica papaya, emerges as a promising candidate for green nanotechnology-based applications due to its diverse medicinal properties, including anticancer properties. Purpose: This study presents a novel approach in nanomedicine and oncology, exploring the potential of green nanotechnology by developing and evaluating technetium-99m radiolabeled papain nanoparticles (99mTc-P-NPs) for imaging breast tumors. The study aimed to investigate the efficacy and specificity of these nanoparticles in breast cancer models through preclinical in vitro and in vivo assessments. Methods: Papain nanoparticles (P-NPs) were synthesized using a radiation-driven method and underwent thorough characterization, including size, surface morphology, surface charge, and cytotoxicity assessment. Subsequently, P-NPs were radiolabeled with technetium-99m (99mTc), and in vitro and in vivo studies were conducted to evaluate cellular uptake at tumor sites, along with biodistribution, SPECT/CT imaging, autoradiography, and immunohistochemistry assays, using breast cancer models. Results: The synthesized P-NPs exhibited a size mean diameter of 9.3 ± 1.9 nm and a spherical shape. The in vitro cytotoxic activity of native papain and P-NPs showed low cytotoxicity in HUVEC, MDA-MB231, and 4T1 cells. The achieved radiochemical yield was 94.2 ± 3.1% that were sufficiently stable (≥90%) for 6 h. The tumor uptake achieved in the 4T1 model was 2.49 ± 0.32% IA/g at 2 h and 1.51 ± 0.20% IA/g at 6 h. In the spontaneous breast cancer model, 1.19 ± 0.20% IA/g at 2 h and 0.86 ± 0.31% IA/g at 6 h. SPECT/CT imaging has shown substantial tumor uptake of the new nanoradiopharmaceutical and clear tumor visualization. 99mTc-P-NPs exhibited a high affinity to tumoral cells confirmed by ex vivo autoradiography and immunohistochemistry assays. Conclusion: The findings underscore the potential of green nanotechnology-driven papain nanoparticles as promising agents for molecular imaging of breast and other tumors through SPECT/CT imaging. The results represent a substantial step forward in the application of papain nanoparticles as carriers of diagnostic and therapeutic radionuclides to deliver diagnostic/therapeutic payloads site-specifically to tumor sites for the development of a new generation of nanoradiopharmaceuticals.

Advances in silver nanoparticles: a comprehensive review on their potential as antimicrobial agents and their mechanisms of action elucidated by proteomics.

Nanoparticles play a crucial role in the field of nanotechnology, offering different properties due to their surface area attributed to their small size. Among them, silver nanoparticles (AgNPs) have attracted significant attention due to their antimicrobial properties, with applications that date back from ancient medicinal practices to contemporary commercial products containing ions or silver nanoparticles. AgNPs possess broad-spectrum biocidal potential against bacteria, fungi, viruses, and Mycobacterium, in addition to exhibiting synergistic effects when combined with certain antibiotics. The mechanisms underlying its antimicrobial action include the generation of oxygen-reactive species, damage to DNA, rupture of bacterial cell membranes and inhibition of protein synthesis. Recent studies have highlighted the effectiveness of AgNPs against various clinically relevant bacterial strains through their potential to combat antibiotic-resistant pathogens. This review investigates the proteomic mechanisms by which AgNPs exert their antimicrobial effects, with a special focus on their activity against planktonic bacteria and in biofilms. Furthermore, it discusses the biomedical applications of AgNPs and their potential non-preparation of antibiotic formulations, also addressing the issue of resistance to antibiotics.

Use of Sugar Cane Bagasse as Solid Extraction Phase Sorbent to Analyze Hormones from Industrial Effluent.

Sugar cane bagasse (SCB) is an abundant byproduct of sugar and bioethanol mills. It has been effectively used as a low-cost biosorbent to remove hazardous chemical compounds from a variety of effluent sources. Herein, we report on the preparation of SCB and its use as a solid phase extraction (SPE) sorbent to retain synthetic hormones (ethinylestradiol, drospirenone, and levonorgestrel) from industrial pharmaceutical plant effluent samples prior to LC-MS/MS quantitative analysis. We evaluated the reproducibility and recoveries and accuracy data analyses were compared with that of commercial SPE (cSPE) cartridges. The results from the evaluated parameters indicated that the SCB bed had an efficiency of >99%, comparable to that of cSPE cartridges, demonstrating the applicability and feasibility of this material as an effective and green chemistry alternative, as well as its biosorbent potential to remove hormones from industrial pharmaceutical effluent.

The State of the Art of Theranostic Nanomaterials for Lung, Breast, and Prostate Cancers.

The synthesis and engineering of nanomaterials offer more robust systems for the treatment of cancer, with technologies that combine therapy with imaging diagnostic tools in the so-called nanotheranostics. Among the most studied systems, there are quantum dots, liposomes, polymeric nanoparticles, inorganic nanoparticles, magnetic nanoparticles, dendrimers, and gold nanoparticles. Most of the advantages of nanomaterials over the classic anticancer therapies come from their optimal size, which prevents the elimination by the kidneys and enhances their permeation in the tumor due to the abnormal blood vessels present in cancer tissues. Furthermore, the drug delivery and the contrast efficiency for imaging are enhanced, especially due to the increased surface area and the selective accumulation in the desired tissues. This property leads to the reduced drug dose necessary to exert the desired effect and for a longer action within the tumor. Finally, they are made so that there is no degradation into toxic byproducts and have a lower immune response triggering. In this article, we intend to review and discuss the state-of-the-art regarding the use of nanomaterials as therapeutic and diagnostic tools for lung, breast, and prostate cancer, as they are among the most prevalent worldwide.

Species-Specific in vitro and in vivo Evaluation of Toxicity of Silver Nanoparticles Stabilized with Gum Arabic Protein.

INTRODUCTION: We report, herein, in vitro, and in vivo toxicity evaluation of silver nanoparticles stabilized with gum arabic protein (AgNP-GP) in Daphnia similis, Danio rerio embryos and in Sprague Dawley rats. PURPOSE: The objective of this investigation was to evaluate in vitro and in vivo toxicity of silver nanoparticles stabilized with gum arabic protein (AgNP-GP), in multispecies due to the recognition that toxicity evaluations beyond a single species reflect the environmental realism. In the present study, AgNP-GP was synthesized through the reduction of silver salt using the tri-alanine-phosphine peptide (commonly referred to as "Katti Peptide") and stabilized using gum arabic protein. METHODS: In vitro cytotoxicity tests were performed according to ISO 10993-5 protocols to assess cytotoxicity index (IC50) values. Acute ecotoxicity (EC50) studies were performed using Daphnia similis, according to the ABNT NBR 15088 protocols. In vivo toxicity also included evaluation of acute embryotoxicity using Danio rerio (zebrafish) embryos following the OECD No. 236 guidelines. We also used Sprague Dawley rats to assess the toxicity of AgNP-GP in doses from 2.5 to 10.0 mg kg-1 body weight. RESULTS: AgNP-GP nanoparticles were characterized through UV (405 nm), core size (20±5 nm through TEM), hydrodynamic size (70-80 nm), Zeta (ζ) potential (- 26 mV) using DLS and Powder X ray diffraction (PXRD) and EDS. PXRD showed pattern consistent with the Ag (1 1 1) peak. EC50 in Daphnia similis was 4.40 (3.59-5.40) µg L-1. In the zebrafish species, LC50 was 177 µg L-1. Oral administration of AgNP-GP in Sprague Dawley rats for a period of 28 days revealed no adverse effects in doses of up to 10.0 mg kg-1 b.w. in both male and female animals. CONCLUSION: The non-toxicity of AgNP-GP in rats offers a myriad of applications of AgNP-GP in health and hygiene for use as antibiotics, antimicrobial and antifungal agents.