Enhanced nanoparticle uptake into virus infected cells: Could nanoparticles be useful in antiviral therapy?

Abstract

Virus infections cause diseases of different severity ranged from mild infection e.g. common cold into life threatening diseases e.g. Human Immunodeficiency virus (HIV), Hepatitis B. Virus infections represent 44% of newly emerging infections. Although there are many efficient antiviral agents, they still have drawbacks due to accumulation at off target organs and developing of virus resistance due to virus mutation. Therefore, developing a delivery system that can selectively target drug into affected organs and avoid off target accumulation would be a highly advantageous strategy to improve antiviral therapy. Nanoparticles (NP) can be effectively targeted to the liver, and therefore it could be used for improving therapy of hepatic virus infections including hepatitis B virus and hepatitis C virus (HCV). Many studies were performed to encapsulate antiviral agents into nano-delivery system to improve their pharmacokinetics parameters to have a better therapeutic efficacy with lower side effects. However, the effect of virus infection on the uptake of NP has not yet been studied in detail. The latter is a crucial area as modulation of endocytic uptake of nanoparticles could impact on reduce potential therapeutic usefulness of antiviral agents loaded into nano-delivery system. In this study, a fluorescently-labelled polymeric nanoparticle was prepared and used to track NP uptake into Huh7.5, human hepatoma cells transfected with replicating HCV genomes, compared with non-transfected cells as a model representing hepatocyte uptake. Confocal microscopy and flow cytometry of virus transfected Huh7.5 cells unexpectedly demonstrated two-fold increase in uptake of NP compared to non-transfected cells. Therefore, virus transfection enhanced NP uptake into Huh7.5 cells and NP could be considered as a promising delivery system for targeted treatment of hepatitis viruses.

Phytosynthesized Metallic Nanoparticles—between Nanomedicine and Toxicology. A Brief Review of 2019′s Findings

“…In spite the numerous advantages of this approach, the process still has some bottle-necks, the most important of which is represented by the difficulties in obtaining homogenous nanoparticles in terms of shape and, especially, size, as well as the elucidation of the specificity of individual biomolecules [3]. Though several types of metallic nanoparticles that are synthesized by using plant extracts have been studied target organisms (leading to their proposal as antimicrobial [4], antiviral [5] or cytogenotoxic agents [6]), their possible negative toxicity has not been thoroughly established. The present review aims to present the advances that have been recorded in the last year in the area of phytosynthesized nanoparticle applications and toxicity studies, as well to underline the shortcomings of the encountered approach.…”

“…However, this increasing interest has not been not reflected in the studies regarding the toxicological effects of nanoparticles (NPs); this should be a subject of greatest interest, as the increasing administration of NPs in general (and phytosynthesized NPs in particular) could lead to their accumulation in the environment (soil, water and living organisms). The present review aims to present the most recent findings in the application of phytosynthesized NPs as antimicrobial and antitumoral agents, as well as the results regarding their toxicological potential.Materials 2020, 13, 574 2 of 32 in terms of their toxic potential towards target organisms (leading to their proposal as antimicrobial [4], antiviral [5] or cytogenotoxic agents [6]), their possible negative toxicity has not been thoroughly established. The present review aims to present the advances that have been recorded in the last year in the area of phytosynthesized nanoparticle applications and toxicity studies, as well to underline the shortcomings of the encountered approach.…”

“…Materials 2020, 13, 574 2 of 32 in terms of their toxic potential towards target organisms (leading to their proposal as antimicrobial [4], antiviral [5] or cytogenotoxic agents [6]), their possible negative toxicity has not been thoroughly established. The present review aims to present the advances that have been recorded in the last year in the area of phytosynthesized nanoparticle applications and toxicity studies, as well to underline the shortcomings of the encountered approach.…”

Polyglycerol Hyperbranched Polyesters: Synthesis, Properties and Pharmaceutical and Biomedical Applications

“…Nanoparticles can be effectively targeted to the liver, and therefore could be used for improving the therapy of hepatic virus infections including hepatitis B and hepatitis C. A fluorescently-labelled linear PGAd polymeric nanoparticle was prepared and used to track NP uptake into human hepatoma cells transfected with replicating hepatitis C virus genomes (Huh7.5), compared with non-transfected cells as a model representing hepatocyte uptake [62]. Confocal microscopy and flow cytometry demonstrated a two-fold increase in uptake of NP in transfected cells compared to non-transfected ones.…”

“…One of the advantages of linear PGAd over PLA and PLGA, which are extensively used in biomedical applications, is the possibility to modify the pendent hydroxyl groups on the polymer backbone with a variety of acyl groups to change the hydrophobicity of the polymer. It is a smart strategy to produce polymers with completely different properties, based on the kind of acyl moieties used [10,42,58,59,62]. The physicochemical properties of the polymer can be adjusted according to the requirements of different drugs (hydrophilic or hydrophobic) allowing various drug incorporations.…”