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Background/Objectives: Upon systemic delivery, macrophages take up a significant portion of nanoparticles and may become saturated. The saturation of macrophages may pose risks to overall immune function and signaling pathways. While some information is available on the survival and functionality of macrophages upon saturation with nanoparticles, there is limited understanding of the molecular-level changes that can occur and their corresponding influences on macrophage phenotypes, gene expression, and immune signaling pathways. Methods: In this study, RAW 264.7 macrophages were saturated with silica nanoparticles (SNPs) of different sizes (50 and 100 nm), porosities (nonporous, mesoporous), densities (solid, mesoporous, and hollow), and surface compositions (hydrophobicity) at their maximum non-toxic concentrations. The saturated macrophages were evaluated for changes in gene expression and immune signaling pathways by RNA sequencing, weighted gene co-expression network analysis (WGCNA), and Hallmark and KEGG pathway analyses. Results: Our results show that in the range studied, the particle size did not have a significant effect on the gene expression profile. Porous SNPs of comparable sizes resulted in increased and unique changes in the gene expression profile compared to nonporous SNPs. Major immune signaling pathways, including TNF-alpha signaling via NF-κB pathways, mTORC1 signaling, and p53 pathways, were modulated in SNP-saturated macrophages. This modulation depended on the physicochemical properties of the particles. The Th1/Th2 multiplex immunoassay revealed that the uptake of SNPs increases the amount of the TNF-alpha cytokine compared to the nontreated controls, whereas no changes in IL-6 and IL-12p70 pro-inflammatory cytokines were observed. Conclusions: Our results demonstrate that physicochemical properties of SNPs, such as porosity, size, surface functionality, and density, influence the modulation of gene expression and macrophage immune signaling pathways. These results, along with others, can provide guidance on the selection of silica nanoparticles for the safe and effective systemic delivery of bioactive agents.

The emergence of nanotechnology offers a promising avenue for enhancing cancer treatment outcomes. In this context, biomimetic nanoparticles have emerged as an exciting frontier in the field of biomedicine. These nanoparticles can emulate essential biological functions, drawing from an abundant reservoir of cellular capabilities. This includes engaging in biological binding, precise homing to tumor sites, and interaction with immune cells. These inherent traits endow biomimetic nanoparticles with a suite of intelligent features, including biocompatibility, low immunogenicity, reduced toxicity, immune evasion, prolonged circulation, homotypic binding, enhanced tumor targeting, and the capability of precise delivery. By integrating biologically inspired coatings derived from cell membranes with nanoparticle cores, these carriers become highly versatile vessels for encapsulating a wide array of therapeutic agents. As a result, they are being extensively harnessed for the precise delivery of drugs and genes, underpinning numerous biomedical applications. This discussion delves into the challenges and opportunities presented by biomimetic nanoparticles and offers a comprehensive exploration of their fundamentals and recent breakthroughs, with an eye towards clinical translation. By bridging the gap between scientific innovation and clinical utility, biomimetic nanoparticles hold great promise for advancing the field of cancer treatment.

Ovarian cancer, which is one of the most diagnosed cancer types among women, maintains its significance as a global health problem. Several drug candidates have been investigated for the potential treatment of ovarian cancer. Nonsteroidal anti-inflammatory drugs (NSAIDs) demonstrated anti-cancer activity through the inhibition of cyclooxygenase 2 (COX-2) and by inhibiting COX-2-dependent prostaglandin (PG) production. Naproxen is one of the most used NSAIDs and Naproxen-derived compounds (NDCs) may show potential treatment effects on cancer as chemotherapeutic drugs. Although there are successful drug development studies, the lack of solubility of these drug candidates in aqueous media results in limited bioavailability and high variability of patient responses during treatment. Low aqueous solubility is one of the main problems in the pharmaceutical industry in terms of drug development. Nanotechnology-based strategies provide solutions to hydrophobic drug limitations by increasing dispersion and improving internalization. In this study, two different NDCs (NDC-1 and NDC-2) bearing a thiosemicarbazide/1,2,4-triazole moiety were synthesized and tested for chemotherapeutic effects on ovarian cancer cells, which have a high COX-2 expression. To overcome the limited dispersion of these hydrophobic drugs, the drug molecules were conjugated to the surface of 13 nm AuNPs. Conjugation of drugs to AuNPs increased the distribution of drugs in aqueous media, and NDC@AuNP conjugates exhibited excellent colloidal stability for up to 8 weeks. The proposed system demonstrated an increased chemotherapeutic effect than the free drug counterparts with at least 5 times lower IC50 values. NDC@AuNP nanosystems induced higher apoptosis rates, which established a simple and novel way to investigate activity of prospective drugs in drug discovery research.

COVID-19 has caused millions of cases and deaths all over the world since late 2019. Rapid detection of the virus is crucial for controlling its spread through a population. COVID-19 is currently detected by nucleic acid-based tests and serological tests. However, these methods have limitations such as the requirement of high-cost reagents, false negative results and being time consuming. Surface-enhanced Raman scattering (SERS), which is a powerful technique that enhances the Raman signals of molecules using plasmonic nanostructures, can overcome these disadvantages. In this study, we developed a virus-infected cell model and analyzed this model by SERS combined with Principal Component Analysis (PCA). HEK293 cells were transfected with plasmids encoding the nucleocapsid (N), membrane (M) and envelope (E) proteins of SARS-CoV-2 via polyethyleneimine (PEI). Non-plasmid transfected HEK293 cells were used as the control group. Cellular uptake was optimized with green fluorescence protein (GFP) plasmids and evaluated by fluorescence microscopy and flow cytometry. The transfection efficiency was found to be around 60%. The expression of M, N, and E proteins was demonstrated by western blotting. The SERS spectra of the total proteins of transfected cells were obtained using a gold nanoparticle-based SERS substrate. Proteins of the transfected cells have peak positions at 646, 680, 713, 768, 780, 953, 1014, 1046, 1213, 1243, 1424, 2102, and 2124 cm⁻¹. To reveal spectral differences between plasmid transfected cells and non-transfected control cells, PCA was applied to the spectra. The results demonstrated that SERS coupled with PCA might be a favorable and reliable way to develop a rapid, low-cost, and promising technique for the detection of COVID-19.

There is an ongoing effort to increase the efficiency of gene delivery for the regulation of diseases-related genes. In this report, we demonstrate the efficiency of a DNA-based nanostructure to deliver morpholino antisense oligonucleotides for the upregulated genes in breast cancer as an alternative to the currently used delivery systems. A DNA-tile structure is constructed by embedding antisense oligonucleotides targeting the HER2 and ERα genes. Then, the sticky ends of the DNA-tile nanostructures are hybridized to gold nanoparticles (AuNPs) coated with the complementary oligonucleotides to enhance their cellular uptake. It is found that the morpholino antisense oligonucleotide embedded DNA-tile-AuNPs structure is 30% more effective than the liposome-based system to deliver morpholinos and induce gene silencing in breast cancer cells. The results of the study suggest that the prepared novel nanostructure is an effective and biocompatible carrier that can be used in in vitro gene silencing studies and can be further pursued in in vivo studies.

Background: DNA hybridization allows the preparation of nanoscale DNA structures with desired shape and size. DNA structures using simple base pairing can be used for the delivery of drug molecules into the cells. Since DNA carries multiple negative charges, their cellular uptake efficiency is low. Thus, the modification of the DNA structures with molecules that may enhance the cellular internalization may be an option. Objective: To construct DNA based nanocarrier system and investigate the cellular uptake of DNA tile with/without lactose modification. Methods: Doxorubicin was intercalated to DNA tile and cellular uptake of drug loaded DNA based carrier with/without lactose modification was investigated in vitro. HeLa, BT-474, and MDA-MB-231 cancer cells were used for cellular uptake studies and cytotoxicity assays. Using fluorescence spectroscopy, flow cytometry and confocal microscopy, cellular uptake behavior of DNA tile was investigated. The cytotoxicity of DNA tile structures was determined with WST-1 assay. Results: The results show that modification with lactose effectively increases the intracellular uptake of doxorubicin loaded DNA tile structure by cancer cells compared to the unmodified DNA tile. Conclusion: The findings of this study suggest that DNA based nanostructures modified with carbohydrates can be used as suitable multifunctional nanocarriers with simple chemical modifications.