Robby A. Petros

Bio: Robby A. Petros is an academic researcher from University of North Texas. The author has contributed to research in topics: Systemic acquired resistance & Bioconjugation. The author has an hindex of 11, co-authored 28 publications receiving 3874 citations. Previous affiliations of Robby A. Petros include Texas Woman's University & Columbia University.

Strategies in the design of nanoparticles for therapeutic applications

Abstract: Engineered nanoparticles have the potential to revolutionize the diagnosis and treatment of many diseases; for example, by allowing the targeted delivery of a drug to particular subsets of cells. However, so far, such nanoparticles have not proved capable of surmounting all of the biological barriers required to achieve this goal. Nevertheless, advances in nanoparticle engineering, as well as advances in understanding the importance of nanoparticle characteristics such as size, shape and surface properties for biological interactions, are creating new opportunities for the development of nanoparticles for therapeutic applications. This Review focuses on recent progress important for the rational design of such nanoparticles and discusses the challenges to realizing the potential of nanoparticles.

The complex role of multivalency in nanoparticles targeting the transferrin receptor for cancer therapies.

Abstract: Transferrin receptor (TfR, CD71) has long been a therapeutic target due to its overexpression in many malignant tissues In this study, PRINT nanoparticles were conjugated with TfR ligands for targeted drug delivery Cylindrical poly(ethylene glycol)-based PRINT nanoparticles (diameter (d) = 200 nm, height (h) = 200 nm) labeled with transferrin receptor antibody (NP-OKT9) or human transferrin (NP-hTf) showed highly specific TfR-mediated uptake by all human tumor cell lines tested, relative to negative controls (IgG1 for OKT9 or bovine transferrin (bTf) for hTf) The targeting efficiency was dependent on particle concentration, ligand density, dosing time, and cell surface receptor expression level Interestingly, NP-OKT9 or NP-hTf showed little cytotoxicity on all solid tumor cell lines tested but were very toxic to Ramos B-cell lymphoma, whereas free OKT9 or hTf was not toxic There was a strong correlation between TfR ligand density on the particle surface and cell viability and particle uptake NP-OKT9

An abietane diterpenoid is a potent activator of systemic acquired resistance.

Abstract: Abietane diterpenoids are major constituents of conifer resins that have important industrial and medicinal applications. However, their function in plants is poorly understood. Here we show that dehydroabietinal (DA), an abietane diterpenoid, is an activator of systemic acquired resistance (SAR), which is an inducible defense mechanism that is activated in the distal, non-colonized, organs of a plant that has experienced a local foliar infection. DA was purified as a SAR-activating factor from vascular sap of Arabidopsis thaliana leaves treated with a SAR-inducing microbe. Locally applied DA is translocated through the plant and systemically induces the accumulation of salicylic acid (SA), an important activator of defense, thus leading to enhanced resistance against subsequent infections. The NPR1 (NON-EXPRESSOR OF PR GENES1), FMO1 (FLAVIN-DEPENDENT MONOOXYGENASE1) and DIR1 (DEFECTIVE IN INDUCED RESISTANCE1) genes, which are critical for biologically induced SAR, are also required for the DA-induced SAR, which is further enhanced by azelaic acid, a defense priming molecule. In response to the biological induction of SAR, DA in vascular sap is redistributed into a SAR-inducing 'signaling DA' pool that is associated with a trypsin-sensitive high molecular weight fraction, a finding that suggests that DA-orchestrated SAR involves a vascular sap protein(s).

Signaling by small metabolites in systemic acquired resistance

Abstract: Plants can retain the memory of a prior encounter with a pest. This memory confers upon a plant the ability to subsequently activate defenses more robustly when challenged by a pest. In plants that have retained the memory of a prior, localized, foliar infection by a pathogen, the pathogen-free distal organs develop immunity against subsequent infections by a broad-spectrum of pathogens. The long-term immunity conferred by this mechanism, which is termed systemic acquired resistance (SAR), is inheritable over a few generations. Signaling mediated by the phenolic metabolite salicylic acid (SA) is critical for the manifestation of SAR. Recent studies have described the involvement of additional small metabolites in SAR signaling, including methyl salicylate, the abietane diterpenoid dehydroabietinal, the lysine catabolite pipecolic acid, a glycerol-3-phosphate-dependent factor and the dicarboxylic acid azelaic acid. Many of these metabolites can be systemically transported through the plant and probably facilitate communication by the primary infected tissue with the distal tissues, which is essential for the activation of SAR. Some of these metabolites have been implicated in the SAR-associated rapid activation of defenses in response to subsequent exposure to the pathogen, a mechanism termed priming. Here, we summarize the role of these signaling metabolites in SAR, and the relationship between them and SA signaling in SAR.

Reductively labile PRINT particles for the delivery of doxorubicin to HeLa cells.

Abstract: A Trojan horse PRINT particle composition was developed that incorporates a reductively labile cross-linker to achieve activated release of doxorubicin in vitro. Particles of discrete size and shape (cube side length = 2 micron) containing 30 wt % of a disulfide-based cross-linker and 2 wt % doxorubicin were synthesized. This PRINT composition was shown to release doxorubicin in response to a reducing environment as measured by flow cytometry and was found to be highly proficient at killing HeLa cells in vitro.

Strategies in the design of nanoparticles for therapeutic applications

Abstract: Engineered nanoparticles have the potential to revolutionize the diagnosis and treatment of many diseases; for example, by allowing the targeted delivery of a drug to particular subsets of cells. However, so far, such nanoparticles have not proved capable of surmounting all of the biological barriers required to achieve this goal. Nevertheless, advances in nanoparticle engineering, as well as advances in understanding the importance of nanoparticle characteristics such as size, shape and surface properties for biological interactions, are creating new opportunities for the development of nanoparticles for therapeutic applications. This Review focuses on recent progress important for the rational design of such nanoparticles and discusses the challenges to realizing the potential of nanoparticles.

The effect of nanoparticle size, shape, and surface chemistry on biological systems.

Abstract: An understanding of the interactions between nanoparticles and biological systems is of significant interest. Studies aimed at correlating the properties of nanomaterials such as size, shape, chemical functionality, surface charge, and composition with biomolecular signaling, biological kinetics, transportation, and toxicity in both cell culture and animal experiments are under way. These fundamental studies will provide a foundation for engineering the next generation of nanoscale devices. Here, we provide rationales for these studies, review the current progress in studies of the interactions of nanomaterials with biological systems, and provide a perspective on the long-term implications of these findings.

Mesoporous Silica Nanoparticles: Synthesis, Biocompatibility and Drug Delivery

Abstract: In the past decade, mesoporous silica nanoparticles (MSNs) have attracted more and more attention for their potential biomedical applications. With their tailored mesoporous structure and high surface area, MSNs as drug delivery systems (DDSs) show significant advantages over traditional drug nanocarriers. In this review, we overview the recent progress in the synthesis of MSNs for drug delivery applications. First, we provide an overview of synthesis strategies for fabricating ordered MSNs and hollow/rattle-type MSNs. Then, the in vitro and in vivo biocompatibility and biotranslocation of MSNs are discussed in relation to their chemophysical properties including particle size, surface properties, shape, and structure. The review also highlights the significant achievements in drug delivery using mesoporous silica nanoparticles and their multifunctional counterparts as drug carriers. In particular, the biological barriers for nano-based targeted cancer therapy and MSN-based targeting strategies are discussed. We conclude with our personal perspectives on the directions in which future work in this field might be focused.