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1. Dendritic Polyglycerol‐Derived Nano‐Architectures as Delivery Platforms of Gemcitabine for Pancreatic Cancer

   https://doi.org/10.1002/mabi.201900073  

   Ray, Priyanka ; Ferraro, Magda ; Haag, Rainer ; Quadir, Mohiuddin ( June 2019 , Macromolecular Bioscience)

   Dendritic polyglycerol‐co‐polycaprolactone (PG‐co‐PCL)‐derived block copolymers are synthesized and explored as nanoscale drug delivery platforms for a chemotherapeutic agent, gemcitabine (GEM), which is the cornerstone of therapy for pancreatic ductal adenocarcinoma (PDAC). Current treatment strategies with GEM result in suboptimal therapeutic outcome owing to microenvironmental resistance and rapid metabolic degradation of GEM. To address these challenges, physicochemical and cell‐biological properties of both covalently conjugated and non‐covalently stabilized variants of GEM‐containing PG‐co‐PCL architectures have been evaluated. Self‐assembly behavior, drug loading and release capacity, cytotoxicity, and cellular uptake properties of these constructs in monolayer and in spheroid cultures of PDAC cells are investigated. To realize the covalently conjugated carrier systems, GEM, in conjunction with a tertiary amine, is attached to the polycarbonate block grafted from the PG‐co‐PCL core. It is observed that pH‐dependent ionization properties of these amine side‐chains direct the formation of self‐assembly of block copolymers in the form of nanoparticles. For non‐covalent encapsulation, a facile “solvent‐shifting” technique is adopted. Fabrication techniques are found to control colloidal and cellular properties of GEM‐loaded nanoconstructs. The feasibility and potential of these newly developed architectures for designing carrier systems for GEM to achieve augmented prognosis for pancreatic cancer are reported.

    

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2. Emerging investigator series: polymeric nanocarriers for agricultural applications: synthesis, characterization, and environmental and biological interactions

   https://doi.org/10.1039/C9EN01127G  

   Shakiba, Sheyda ; Astete, Carlos E. ; Paudel, Sachin ; Sabliov, Cristina M. ; Rodrigues, Debora F. ; Louie, Stacey M. ( January 2020 , Environmental Science: Nano)

   null (Ed.)

   Polymeric nanoparticles represent one major class of nanomaterials that has been proposed to improve the sustainability of agricultural operations by delivering organic agrochemicals such as pesticides more efficiently. Polymeric nanoparticles can improve efficiency through improved targeting and uptake, slow release, and lower losses of the chemicals, while also conferring the benefits of biodegradability and biocompatibility. This review provides a tutorial to environmental nanotechnology researchers interested in initiating research on the development and application of polymeric nanocarriers for delivery of agrochemicals, including pesticides and growth promoters for crops and antibiotics for livestock. In particular, this review covers the wider suite of methods that will be required beyond those typically used for inorganic metal or metal oxide nanoparticles, including synthesis of custom polymeric nanocarriers and characterization and tuning of agrochemical loading and release profiles. Benefits of polymeric nanocarriers are then discussed in terms of the physicochemical properties and fate and transport behaviors that contribute to higher efficiency and lesser environmental impacts compared to traditional (non-nano) formulations. Finally, opportunities for environmental nanotechnology researchers to collaborate with material scientists, microbiologists, and agricultural scientists to optimize the development of polymeric nanocarriers for agriculture are discussed. 

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3. Nanoclays in medicine: a new frontier of an ancient medical practice

   https://doi.org/10.1039/d2ma00528j  

   Katti, Kalpana S. ; Jasuja, Haneesh ; Jaswandkar, Sharad V. ; Mohanty, Sibanwita ; Katti, Dinesh R. ( October 2022 , Materials Advances)

   Clays have been used as early as 2500 BC in human civilization for medicinal purposes. The ease of availability, biocompatibility, and versatility of these unique charged 2D structures abundantly available in nature have enabled the extensive applications of clays in human history. Recent advances in the use of clays in nanostructures and as components of polymer clay nanocomposites have exponentially expanded the use of clays in medicine. This review covers the details of structures and biomedical applications of several common clays, including montmorillonite, LAPONITE®, kaolinite, and halloysite. Here we describe the applications of these clays in wound dressings as hemostatic agents in drug delivery of drugs for cancer and other diseases and tissue engineering. Also reviewed are recent experimental and modeling studies that elucidate the impact of clay structures on cellular processes and cell adhesion processes. Various mechanisms of clay-mediated bioactivity, including protein localization, modulation of cell adhesion, biomineralization, and the potential of clay nanoparticles to impact cell differentiation, are presented. We also review the current developments in understanding the impact of clays on cellular responses. This review also elucidates new emerging areas of use of nanoclays in osteogenesis and the development of in vitro models of bone metastasis of cancer. 

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4. A novel viral strategy for host factor recruitment: The co-opted proteasomal Rpn11 protein interaction hub in cooperation with subverted actin filaments are targeted to deliver cytosolic host factors for viral replication

   https://doi.org/10.1371/journal.ppat.1009680  

   Molho, Melissa ; Lin, Wenwu ; Nagy, Peter D. ( June 2021 , PLOS Pathogens)

   Wang, Aiming (Ed.)

   Positive-strand (+)RNA viruses take advantage of the host cells by subverting a long list of host protein factors and transport vesicles and cellular organelles to build membranous viral replication organelles (VROs) that support robust RNA replication. How RNA viruses accomplish major recruitment tasks of a large number of cellular proteins are intensively studied. In case of tomato bushy stunt virus (TBSV), a single viral replication protein, named p33, carries out most of the recruitment duties. Yet, it is currently unknown how the viral p33 replication protein, which is membrane associated, is capable of the rapid and efficient recruitment of numerous cytosolic host proteins to facilitate the formation of large VROs. In this paper, we show that, TBSV p33 molecules do not recruit each cytosolic host factor one-by-one into VROs, but p33 targets a cytosolic protein interaction hub, namely Rpn11, which interacts with numerous other cytosolic proteins. The highly conserved Rpn11, called POH1 in humans, is the metalloprotease subunit of the proteasome, which couples deubiquitination and degradation of proteasome substrates. However, TBSV takes advantage of a noncanonical function of Rpn11 by exploiting Rpn11’s interaction with highly abundant cytosolic proteins and the actin network. We provide supporting evidence that the co-opted Rpn11 in coordination with the subverted actin network is used for delivering cytosolic proteins, such as glycolytic and fermentation enzymes, which are readily subverted into VROs to produce ATP locally in support of VRO formation, viral replicase complex assembly and viral RNA replication. Using several approaches, including knockdown of Rpn11 level, sequestering Rpn11 from the cytosol into the nucleus in plants or temperature-sensitive mutation in Rpn11 in yeast, we show the inhibition of recruitment of glycolytic and fermentation enzymes into VROs. The Rpn11-assisted recruitment of the cytosolic enzymes by p33, however, also requires the combined and coordinated role of the subverted actin network. Accordingly, stabilization of the actin filaments by expression of the Legionella VipA effector in yeast and plant, or via a mutation of ACT1 in yeast resulted in more efficient and rapid recruitment of Rpn11 and the selected glycolytic and fermentation enzymes into VROs. On the contrary, destruction of the actin filaments via expression of the Legionella RavK effector led to poor recruitment of Rpn11 and glycolytic and fermentation enzymes. Finally, we confirmed the key roles of Rpn11 and the actin filaments in situ ATP production within TBSV VROs via using a FRET-based ATP-biosensor. The novel emerging theme is that TBSV targets Rpn11 cytosolic protein interaction hub driven by the p33 replication protein and aided by the subverted actin filaments to deliver several co-opted cytosolic pro-viral factors for robust replication within VROs. 

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5. Cell Penetrating Peptides, Novel Vectors for Gene Therapy

   https://doi.org/10.3390/pharmaceutics12030225  

   Taylor, Rebecca E. ; Zahid, Maliha ( March 2020 , Pharmaceutics)

   null (Ed.)

   Cell penetrating peptides (CPPs), also known as protein transduction domains (PTDs), first identified ~25 years ago, are small, 6–30 amino acid long, synthetic, or naturally occurring peptides, able to carry variety of cargoes across the cellular membranes in an intact, functional form. Since their initial description and characterization, the field of cell penetrating peptides as vectors has exploded. The cargoes they can deliver range from other small peptides, full-length proteins, nucleic acids including RNA and DNA, liposomes, nanoparticles, and viral particles as well as radioisotopes and other fluorescent probes for imaging purposes. In this review, we will focus briefly on their history, classification system, and mechanism of transduction followed by a summary of the existing literature on use of CPPs as gene delivery vectors either in the form of modified viruses, plasmid DNA, small interfering RNA, oligonucleotides, full-length genes, DNA origami or peptide nucleic acids. 

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