Nanocarrier-based delivery systems can be used to increase the safety and efficacy of active ingredients in medical, veterinary, or agricultural applications, particularly when such ingredients are unstable, sparingly soluble, or cause off-target effects. In this review, we highlight the diversity of nanocarrier materials and their key advantages compared to free active ingredients. We discuss current trends based on peer-reviewed research articles, patent applications, clinical trials, and the nanocarrier formulations already approved by regulatory bodies. Although most nanocarriers have been engineered to combat cancer, the number of formulations developed for other purposes is growing rapidly, especially those for the treatment of infectious diseases and parasites affecting humans, livestock, and companion animals. The regulation and prohibition of many pesticides have also fueled research to develop targeted pesticide delivery systems based on nanocarriers, which maximize efficacy while minimizing the environmental impact of agrochemicals.
Platform technologies based on plant virus nano-particles (VNPs) and virus-like particles (VLPs) are attracting the attention of researchers and clinicians because the particles are biocompatible, biodegradable, noninfectious in mammals, and can readily be chemically and genetically engineered to carry imaging agents and drugs. When the Physalis mottle virus (PhMV) coat protein is expressed in Escherichia coli, the resulting VLPs are nearly identical to the viruses formed in vivo. Here, we isolated PhMV-derived VLPs from ClearColi cells and carried out external and internal surface modification with fluorophores using reactive lysine-N-hydroxysuccinimide ester and cysteine-maleimide chemistries, respectively. The uptake of dye-labeled particles was tested in a range of cancer cells and monitored by confocal microscopy and flow cytometry. VLPs labeled internally on cysteine residues were taken up with high efficiency by several cancer cell lines and were colocalized with the endolysosomal marker LAMP-1 within 6 h, whereas VLPs labeled externally on lysine residues were taken up with lower efficiency, probably reflecting differences in surface charge and the propensity to bind to the cell surface. The infusion of dye and drug molecules into the cavity of the VLPs revealed that the photosensitizer (PS), Zn-EpPor, and the drugs crystal violet, mitoxantrone (MTX), and doxorubicin (DOX) associated stably with the carrier via noncovalent interactions. We confirmed the cytotoxicity of the PS-PhMV and DOX-PhMV particles against prostate cancer, ovarian and breast cancer cell lines, respectively. Our results show that PhMV-derived VLPs provide a new platform technology for the delivery of imaging agents and drugs, with preferential uptake into cancer cells. These particles could therefore be developed as multifunctional tools for cancer diagnosis and therapy.
Plant parasitic nematodes are a major burden to the global agricultural industry, causing a $157 billion loss each year in crop production worldwide. Effective treatment requires large doses of nematicides to be applied, putting the environment and human health at risk. Challenges are to treat nematodes that are located deep within the soil, feeding on the roots of plants. To attack the problem at its roots, we propose the use of tobacco mild green mosaic virus (TMGMV), an EPA-approved herbicide as a carrier to deliver nematicides. TMGMV self-assembles into a 300 × 18 nm soft matter nanorod with a 4 nm-wide hollow channel. This plant virus is comprised of 2130 identical coat protein subunits, each of which displays solvent-exposed carboxylate groups from Glu/Asp as well as Tyr side chains, enabling the functionalization of the carrier with cargo. We report (1) the successful formulation and characterization of TMGMV loaded with ∼1500 copies of the anthelmintic drug crystal violet (CV), (2) the bioavailability and treatment efficacy of TMGMV vs CV to nematodes in liquid cultures, and (3) the superior soil mobility ofTMGMV compared to free CV.
Large doses of chemical pesticides are required to achieve effective concentrations in the rhizosphere, which results in the accumulation of harmful residues. Precision farming is needed to improve the efficacy of pesticides, but also to avoid environmental pollution, and slow-release formulations based on nanoparticles offer one solution. Here, we tested the mobility of synthetic and virus-based model nanopesticides by combining soil column experiments with computational modelling. We found that the tobacco mild green mosaic virus and cowpea mosaic virus penetrate soil to a depth of at least 30 cm, and could therefore deliver nematicides to the rhizosphere, whereas the Physalis mosaic virus remains in the first 4 cm of soil and would be more useful for the delivery of herbicides. Our experiments confirm that plant viruses are superior to synthetic Reprints and permissions information is available at www.nature.com/reprints.
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