Targets

Hepatocellular carcinoma is a pressing global health issue, ranking as the third leading cause of cancer-related mortality in humans. Chronic liver diseases, such as hepatitis B and C infections and cirrhosis, are often associated with hepatocellular carcinoma, necessitating ongoing research for improved diagnostic and therapeutic strategies. Animal models, including both spontaneous and chemically induced models like diethylnitrosamine, play a pivotal role in understanding hepatocellular carcinoma mechanisms. Metabolic alterations in tumoral hepatocytes contribute significantly to cancer initiation and progression, impacting energy metabolism and cell survival. Lectins, specifically Concanavalin A, provide valuable insights into altered glycosylation patterns in cancer cells. This study employs lectin histochemistry to assess hepatic alterations in Concanavalin A expression in a murine model of diethylnitrosamine-induced hepatocellular carcinoma. Utilizing confocal laser scanning microscopy, our study unveils notable changes in Concanavalin A subcellular localization and intensity distribution in hepatocellular carcinoma compared with healthy liver tissue. A significant increase in the Concanavalin A labeling within the tumoral cells and a shifting of the expression within the perinuclear space is observed. These findings offer valuable insights into molecular changes in hepatocellular carcinoma, providing potential avenues for diagnostic and therapeutic advancements. Full article

Phycobiliproteins (PBPs) are accessory light-harvesting pigment complexes found in cyanobacteria, red algae, and certain types of cryptophytes. The unique spectral features (strong absorbance and fluorescence), proteinaceous nature, and some imperative properties such as the anti-oxidative, hepato-protective, anti-inflammatory, and anti-aging activity of PBPs allow their use in biomedical industries. However, basic research and technological innovations are required to explore their potential in biomedical applications. The techniques responsible for therapeutic effects need to be standardized for medical application purposes. This review focuses on the current status of PBPs, their structure, functions, methods of preparation, and applications. Additionally, the stability, bioavailability, and safety issues of PBPs, along with their use in therapeutics, are discussed. Full article

Cell-surface glycans are abundant and complex and play a critical role in maintaining protein stability, regulating cell behavior, and participating in cell communication. Obtaining structural information on glycans in situ is helpful to further understand the role of glycans in the physiological and pathological processes of cells and the regulatory mechanism. To achieve this, we can use recognition or labeling strategies to convert the presence of glycans on the cell surface into signals that can be detected. Currently, many different types of in situ sensing strategies for glycans have been developed. The spatial control of the conversion process can realize the restriction of glycan detection to specific proteins, and the introduction of signal amplification technology into the conversion process can improve the sensitivity of sensing. In this paper, the recent progress of glycan labeling methods and sensing technology is reviewed, and the future development direction is prospected. Full article

The sensitive and effective detection of microRNAs (miRNAs) is of great significance since miRNAs have been proven to have undeniable importance in participating in many biological processes. Herein, we present a novel, sensitive, label-free electrochemical miRNA detection method. Three signal amplification techniques are incorporated in this method, including the efficient conjugate of primer-modified polystyrene spheres (PS) with magnetic beads (MBs) triggered by target miRNA, template-free surface-initiated enzymatic polymerization (SIEP) on the primers, and the use of copper ions in square wave voltammetry (SWV) for detecting acidically depurinated primers. Cooperating with the electrochemical approach, this method was able to achieve a detection limit of 120 aM. With an attomole level of sensitivity and easiness of manipulation, this novel method is suitable for miRNA routine detection in both research and clinical aspects. Full article

RNA interference (RNAi) therapy is a promising approach for cancer therapy. However, due to the weak binding affinity between a carrier and small interference RNA (siRNA) and complicated tumor environment, efficient loading and release of siRNA still remain challenging. Here, we design photo-cleavable polycations-wrapped upconversion nanoparticles (PC-UCNPs) for spatially and temporally controllable siRNA delivery. The PC-UCNPs are synthesized by in situ reversible addition−fragmentation chain transfer (RAFT) polymerization of photo-cleaved 5-(2-(dimethylamino)ethoxy)-2-nitrobenzyl acrylat (MENA) monomer and poly(oligo(ethylene oxide) methyl ether acrylate (OEMA) mononer through a chain transfer agent that anchored on the surface of silica-coated upconversion nanoparticles (UCNPs@SiO₂). After reacting with CH₃I, siRNA and hyaluronic acid (HA) are adsorbed on the particle surface to prepare PC-UCNPs/siRNA/HA. The reaction with cell-secreted hyaluronidase (HAase) achieves the intracellular delivery of PC-UCNPs/siRNA/HA, and 980 nm laser irradiation causes siRNA release, which effectively improves the gene silencing efficiency in vitro and suppresses tumor growth in vivo; therefore, these processes have a promising potential application in precision medicine. Full article

A near-IR BODIPY was covalently conjugated via its isothiocyanate groups to one or two Erlotinib molecules, a known tyrosine kinase inhibitor (TKI), via triethylene glycol spacers, to produce two novel BODIPY-monoTKI and BODIPY-diTKI conjugates. The ability of these conjugates to target the intracellular domain of the epidermal growth factor receptor (EGFR) was investigated using molecular modeling, surface plasma resonance (SPR), EGFR kinase binding assay, time-dependent cellular uptake, and fluorescence microscopy. While both the BODIPY-monoTKI and the BODIPY-diTKI conjugates were shown to bind to the EGFR kinase by SPR and accumulated more efficiently within human HEp2 cells that over-express EGFR than BODIPY alone, only the BODIPY-monoTKI exhibited kinase inhibition activity. This is due to the high hydrophobic character and aggregation behavior of the BODIPY-diTKI in aqueous solutions, as shown by fluorescence quenching. Furthermore, the competition of the two Erlotinibs in the diTKI conjugate for the active site of the kinase, as suggested by computational modeling, might lead to a decrease in binding relative to the monoTKI conjugate. Nevertheless, the efficient cellular uptake and intracellular localization of both conjugates with no observed cytotoxicity suggest that both could be used as near-IR fluorescent markers for cells that over-express EGFR. Full article

Telomerase represents an essential molecular machinery for tumor occurrence and progression and a potential therapeutic target for cancer treatment. Sensitive and reliable analysis of telomerase activity is of significant importance for the diagnosis and treatment of cancer. In this study, we developed a telomerase-activated nanoscintillator probe for deep-tissue and background-free imaging of telomerase activity and screening telomerase inhibitors in tumor-bearing living mice models. The probe was constructed by modifying lanthanide-doped nanoscintillators with aptamer-containing DNA anchor strands which hybridized with quencher labelled–oligonucleotide strands and telomerase primers. The X-ray-induced fluorescence of the probe was quenched originally but turned on upon telomerase-catalyzed extension of the primer. Benefiting from exceptional tissue penetrating properties and negligible autofluorescence of X-ray excitation, this probe enabled direct detection of telomerase activity in vivo via fluorescence imaging. Furthermore, with the direct, readable fluorescent signals, the probe enabled the screening of telomerase inhibitors in living cells and whole-animal models in the native states of telomerase. This strategy would inspire the development of low autofluorescence and deep tissue bioimaging probes for disease diagnosis and drug development in high-level living settings. Full article

The onset of brain diseases has a terrible impact on people’s lives, including brain tumors, Alzheimer’s disease, Parkinson’s disease, depression, and schizophrenia. Thus, the diagnosis and treatment of various brain disorders have been receiving specific attention. The fluorescence imaging technique is useful for examining brain diseases because it is intuitive, in situ, and real-time. Therefore, fluorescent imaging has so far been successfully employed to identify molecules associated with brain disease. In this review, the last five years of research advancements in fluorescent imaging agents for the above diseases are summarized, and the creation of pertinent fluorescence probes is described and prospected. Full article