Biliary tract cancers (BTCs) are aggressive malignancies with a dismal prognosis that require intensive targeted therapy. Approximately 10% of BTCs have PBRM1 mutations, which impede DNA damage repair pathways and make cancer cells more susceptible to DNA-damaging chemicals. This review focus on development of poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles targeting delivery system to selectively deliver chemotherapy into PBRM1-deficient BTC cells. These nanoparticles improve therapy efficacy by increasing medication targeting and retention at tumour locations. In preclinical studies, pharmacokinetic profile of this nanoparticle was encouraging and supported its ability to achieve extended circulation time with high drug accumulation in tumor. The review also highlights potential of Pou3F3:I54N to expedite bioassays for patient selection in BTC targeted therapies.

UNASSIGNED: Polymeric nanoparticles used for antigen delivery against infections and for cancer immunotherapy are an emerging therapeutic strategy in promoting the development of innovative vaccines. Beyond their capability to create targeted delivery systems with controlled release of payloads, biodegradable polymers are utilized for their ability to enhance the immunogenicity and stability of antigens.
UNASSIGNED: This review extensively discusses the physicochemical parameters that affect the behavior of nanoparticles as antigen-delivery systems. Additionally, various types of natural and synthetic polymers and recent advancements in nanoparticle-based targeted vaccine production are reviewed.
UNASSIGNED: Biodegradable polymeric nanoparticles have gained major interest in the vaccination filed and have been extensively used to encapsulate antigens against a wide variety of tumors. Moreover, their versatility in terms of tunning their physicochemical characteristics, and their surface, facilitates the targeting to antigen presenting cells and enhances immune response.

UNASSIGNED: In recent years, chimeric antigen receptor T (CAR-T) cell therapy has resulted in a breakthrough in the treatment of patients with refractory or relapsed hematological malignancies. However, the identification of patients suitable for CAR-T cell therapy needs to be improved.
UNASSIGNED: CAR-T cell therapy has demonstrated excellent efficacy in hematological malignancies; however, views on determining when to apply CAR-T cells in terms of the evaluation of patient characteristics remain controversial.
UNASSIGNED: We reviewed the current feasibility and challenges of CAR-T cell therapy in the most common hematological malignancies and classified them according to disease type and treatment priority, to guide clinicians and researchers in applying and investigating CAR-T cells further.

Colorectal cancer (CRC) is one of the most common and challenging malignancy that needs some effective and safer chemotherapeutic agents for the treatment. In this study, anticancer agent epirubicin (Epi) was loaded in polymeric polyethylene glycol-polylactic acid-nanoparticles (mPEG-PLA-NPs) coated with a marine anti-cancer non-toxic polysaccharide fucoidan (FC), to achieve a synergistic activity against CRC. The characterization of the NPs revealed that they were spherical, monodispersed, stable, with a negative zeta potential, and exhibited good biocompatibility and controlled release. In vitro anti-cancer activity of the NPs on HCT116 cell line was found to be promising, and corroborated well with in vivo studies involving BALB/C mice injected with C26 murine cancer cells. The outcome of MTT assay demonstrated that IC50 value of free Epi was 3.72 µM, and that of non-coated and coated Epi nano-formulations was 33.67 and 10.19 µM, respectively. Higher tumor regression, better survival and reduced off-side cardiotoxicity were observed when this novel NPs formulation was used to treat tumor-bearing mice. Free FC and Epi treated mice showed 37.73 % and 61.49 % regression in tumor size, whereas there was 79.76 % and 90.34 % tumor regression in mice treated with non-coated Epi NPs and coated Epi NPs, respectively. Therefore, mPEG-PLA-FC-Epi-NPs hold a potential to be used as an effective chemotherapeutic formulation against CRC, since it exhibited better efficacy and lower toxicity.

The pH- and thermo-responsive behavior of polymeric hydrogels MC-co-MA have been studied in detail using dynamic light scattering DLS, scanning electron microscopy SEM, nuclear magnetic resonance (1H NMR) and rheology to evaluate the conformational changes, swelling-shrinkage, stability, the ability to flow and the diffusion process of nanoparticles at several temperatures. Furthermore, polymeric systems functionalized with acrylic acid MC and acrylamide MA were subjected to a titration process with a calcium chloride CaCl2 solution to analyze its effect on the average particle diameter Dz, polymer structure and the intra- and intermolecular interactions in order to provide a responsive polymer network that can be used as a possible nanocarrier for drug delivery with several benefits. The results confirmed that the structural changes in the sensitive hydrogels are highly dependent on the corresponding critical solution temperature CST of the carboxylic (-COOH) and amide (-CONH2) functional groups and the influence of calcium ions Ca2+ on the formation or breaking of hydrogen bonds, as well as the decrease in electrostatic repulsions generated between the polymer chains contributing to a particle agglomeration phenomenon. The temperature leads to a re-arrangement of the polymer chains, affecting the viscoelastic properties of the hydrogels. In addition, the diffusion coefficients D of nanoparticles were evaluated, showing a closeness among with the morphology, shape, size and temperature, resulting in slower diffusions for larger particles size and, conversely, the diffusion in the medium increasing as the polymer size is reduced. Therefore, the hydrogels exhibited a remarkable response to pH and temperature variations in the environment. During this research, the functionality and behavior of the polymeric nanoparticles were observed under different analysis conditions, which revealed notable structural changes and further demonstrated the nanoparticles promising high potential for drug delivery applications. Hence, these results have sparked significant interest in various scientific, industrial and technological fields.

Global health faces an immense burden from infectious diseases caused by viruses and intracellular protozoan parasites such as the coronavirus disease (COVID-19) and malaria, respectively. These pathogens propagate through the infection of human host cells. The first stage of this host cell infection mechanism is cell attachment, which typically involves interactions between the infectious agent and surface components on the host cell membranes, specifically heparan sulfate (HS) and/or sialic acid (SA). Hence, nanoparticles (NPs) which contain or mimic HS/SA that can directly bind to the pathogen surface and inhibit cell infection are emerging as potential candidates for an alternative anti-infection therapeutic strategy. These NPs can be prepared from metals, soft matter (lipid, polymer, and dendrimer), DNA, and carbon-based materials among others and can be designed to include aspects of multivalency, broad-spectrum activity, biocidal mechanisms, and multifunctionality. This review provides an overview of such anti-pathogen nanomedicines beyond drug delivery. Nanoscale inhibitors acting against viruses and obligate intracellular protozoan parasites are discussed. In the future, the availability of broadly applicable nanotherapeutics would allow early tackling of existing and upcoming viral diseases. Invasion inhibitory NPs could also provide urgently needed effective treatments for protozoan parasitic infections.

Antibiotic resistance (ABR) poses a universal concern owing to the widespread use of antibiotics in various sectors. Nanotechnology emerges as a promising solution to combat ABR, offering targeted drug delivery, enhanced bioavailability, reduced toxicity, and stability. This comprehensive review explores concepts of antibiotic resistance, its mechanisms, and multifaceted approaches to combat ABR. The review provides an in-depth exploration of polymeric nanoparticles as advanced drug delivery systems, focusing on strategies for targeting microbial infections and contributing to the fight against ABR. Nanoparticles revolutionize antimicrobial approaches, emphasizing passive and active targeting. The role of various molecules, including small molecules, antimicrobial peptides, proteins, carbohydrates, and stimuli-responsive systems, is being explored in recent research works. The complex comprehension mechanisms of ABR and strategic use of nanotechnology present a promising avenue for advancing antimicrobial tactics, ensuring treatment efficacy, minimizing toxic effects, and mitigating development of ABR. Polymeric nanoparticles, derived from natural or synthetic polymers, are crucial in overcoming ABR. Natural polymers like chitosan and alginate exhibit inherent antibacterial properties, while synthetic polymers such as polylactic acid (PLA), polyethylene glycol (PEG), and polycaprolactone (PCL) can be engineered for specific antibacterial effects. This comprehensive study provides a valuable source of information for researchers, healthcare professionals, and policymakers engaged in the urgent quest to overcome ABR.

Vulvovaginal candidiasis (VVC) alters the innate cervicovaginal immunity, which provides an important barrier against viruses and other infections. The incidence of this disease has not decreased in the last 30 years, so effective treatments are still needed. Nanoparticles (NPs) of cellulose acetate phthalate (CAP) and clotrimazole (CLZ) were prepared by the emulsification-diffusion method. NPs were characterized using dynamic light scattering, atomic force microscopy and differential scanning calorimetry; their release profile was determined by the dialysis bag technique and mucoadhesion was evaluated with the mucin-particle method. The growth inhibition study of Candida albicans was carried out using the plate counting technique. Finally, accelerated physical stability tests of NPs were carried out, both in water and in SVF. The CAP-CLZ NPs had an average diameter of 273.4 nm, a PDI of 0.284, smooth surfaces and spherical shapes. In vitro release of CLZ from the CAP NPs was categorized with the Weibull model as a matrix system in which initial release was rapid and subsequently sustained. The inhibition of C. albicans growth by the CAP-CLZ NPs was greater than that of free CLZ, and the CAP-only NPs had a microbicidal effect on C. albicans. The NPs showed poor mucoadhesiveness, which could lead to studies of their mucopenetration capacities. An accelerated physical stability test revealed the erosion of CAP in aqueous media. A nanoparticulate system was developed and provided sustained release of CLZ, and it combined an antifungal agent with a microbial polymer that exhibited antifungal activity against C. albicans.

The goal of this work is to investigate if the synergistic antifungal activity between cyclosporine A, CsA, and voriconazole, VRZ, increases when both drugs are encapsulated in a nanocarrier as compared when they are free. The preparation and characterization of blank and VRZ and CsA loaded polymeric based PLGA nanoparticles (PLGA, PLGA-PEG, and PLGA+PEG) was a necessary previous step. Using the more suitable NPs, those of PLGA, the antifungal susceptibility tests performed with VRZ-loaded PLGA NPs, show no significant increase of the antifungal activity in comparison to that of free VRZ. However, the synergistic behavior found for the (VRZ+CsA)-loaded PLGA NPs was fourfold stronger than that observed for the two free drugs together. On the other hand, the investigation into the suppression of C. albicans biofilm formation showed that blank PLGA NPs inhibit the biofilm formation at high NPs concentrations. However, a minor effect or even a slight biofilm increase formation was observed at low and moderate NPs concentrations. Therefore, the enhancement of the biofilm inhibition found for the three tested treatments (CsA alone, VRZ alone, and VRZ+CsA) when comparing free and encapsulated drugs, within the therapeutic window, can be attributed to the drug encapsulation approach. Indeed, polymeric PLGA NPs loaded with CsA, VRZ, or VRZ+CsA are more effective at inhibiting the C. albicans biofilm growth than their free counterparts.

BACKGROUND: Cystic Fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein for which there is no cure. One approach to cure CF is to correct the underlying mutations in the CFTR gene. We have used triplex-forming peptide nucleic acids (PNAs) loaded into biodegradable nanoparticles (NPs) in combination with donor DNAs as reagents for correcting mutations associated with genetic diseases including CF. Previously, we demonstrated that PNAs induce recombination between a donor DNA and the CFTR gene, correcting the F508del CFTR mutation in human cystic fibrosis bronchial epithelial cells (CFBE cells) and in a CF murine model leading to improved CFTR function with low off-target effects, however the level of correction was still below the threshold for therapeutic cure.
METHODS: Here, we report the use of next generation, chemically modified gamma PNAs (γPNAs) containing a diethylene glycol substitution at the gamma position for enhanced DNA binding. These modified γPNAs yield enhanced gene correction of F508del mutation in human bronchial epithelial cells (CFBE cells) and in primary nasal epithelial cells from CF mice (NECF cells).
RESULTS: Treatment of CFBE cells and NECF cells grown at air-liquid interface (ALI) by NPs containing γtcPNAs and donor DNA resulted in increased CFTR function measured by short circuit current and improved gene editing (up to 32 %) on analysis of genomic DNA.
CONCLUSIONS: These findings provide the basis for further development of PNA and NP technology for editing of the CFTR gene.