Preeti Misra

Bio: Preeti Misra is an academic researcher from Beth Israel Deaconess Medical Center. The author has contributed to research in topics: Antibacterial activity & Yield (chemistry). The author has an hindex of 17, co-authored 40 publications receiving 5050 citations. Previous affiliations of Preeti Misra include University of Delhi.

Renal clearance of quantum dots.

Abstract: The field of nanotechnology holds great promise for the diagnosis and treatment of human disease. However, the size and charge of most nanoparticles preclude their efficient clearance from the body as intact nanoparticles. Without such clearance or their biodegradation into biologically benign components, toxicity is potentially amplified and radiological imaging is hindered. Using intravenously administered quantum dots in rodents as a model system, we have precisely defined the requirements for renal filtration and urinary excretion of inorganic, metal-containing nanoparticles. Zwitterionic or neutral organic coatings prevented adsorption of serum proteins, which otherwise increased hydrodynamic diameter by >15 nm and prevented renal excretion. A final hydrodynamic diameter <5.5 nm resulted in rapid and efficient urinary excretion and elimination of quantum dots from the body. This study provides a foundation for the design and development of biologically targeted nanoparticles for biomedical applications.

Design considerations for tumour-targeted nanoparticles

Abstract: Inorganic/organic hybrid nanoparticles are potentially useful in biomedicine, but to avoid non-specific background fluorescence and long-term toxicity, they need to be cleared from the body within a reasonable timescale 1 . Previously, we have shown that rigid spherical nanoparticles such as quantum dots can be cleared by the kidneys if they have a hydrodynamic diameter of approximately 5.5 nm and a zwitterionic surface charge 2 . Here, we show that quantum dots functionalized with highaffinity small-molecule ligands that target tumours can also be cleared by the kidneys if their hydrodynamic diameter is less than this value, which sets an upper limit of 5–10 ligands per quantum dot for renal clearance. Animal models of prostate cancer and melanoma show receptor-specific imaging and renal clearance within 4 h post-injection. This study suggests a set of design rules for the clinical translation of targeted nanoparticles that can be eliminated through the kidneys. Although many classes of biocompatible, inorganic-based nanomaterials have been developed for medical diagnostics and therapeutics 3–7 , many presently available formulations require potentially toxic elements 8 . Efforts have been made to reduce toxicity by modulating the composition, particle shape, physical size and surface coating of the nanoparticles 9 . One common strategy is to engineer nanoparticles using biocompatible and biodegradable polymeric coatings 10–13 . However, polymer coatings generally increase particle

Tissue- and organ-selective biodistribution of NIR fluorescent quantum dots

Abstract: A significant portion of the field of nanomedicine is predicated on being able to target nanoparticles to sites of disease. However, in vivo biodistribution and clearance of nanoparticles are poorly understood. In this study, a novel formulation of near-infrared fluorescent InAs(ZnS) quantum dots was synthesized and coated with a systematically increasing chain length of PEG. We found that varying PEG chain length resulted in major changes in organ/tissue-selective biodistribution and clearance from the body.

Quantitation of CXCR4 Expression in Myocardial Infarction Using 99mTc-Labeled SDF-1α

Abstract: The chemokine stromal-derived factor-1α (SDF-1α, CXCL12) and its receptor CXCR4 are implicated as key mediators of hematopoietic stem cell retention, cancer metastasis, and HIV infection. Their role in myocardial infarction (MI) is not as well defined. The noninvasive in vivo quantitation of CXCR4 expression is central to understanding its importance in these diverse processes as well in the cardiac response to injury. Methods: Recombinant SDF-1α was radiolabeled under aprotic conditions and purified by gel-filtration chromatography (GFC) using high-specific-activity 99mTc-S-acetylmercaptoacetyltriserine-N-hydroxysuccinimide ([99mTc-MAS3]-NHS) prepared by solid-phase preloading. Radiotracer stability and transmetallation under harsh conditions were quantified by GFC. Affinity, specificity, and maximum number of binding sites (Bmax) were quantified, with adenoviral-expressed CXCR4 on nonexpressing cells and endogenous receptor on rat neonatal cardiomyocytes, using a high-throughput live-cell–binding assay. Blood half-life, biodistribution, and clearance of intravenously injected [99mTc-MAS3]-SDF-1α were quantified in Sprague–Dawley rats before and after experimentally induced MI. Results: [99mTc-MAS3]-SDF-1α could be prepared in 2 h total with a specific activity of 8.0 × 107 MBq/mmol (2,166 Ci/mmol) and a radiochemical purity greater than 98%. Degradation of the radiotracer after boiling for 5 min, with and without 1 mM dithiothreitol, and transmetallation in 100% serum at 37°C for 4 h were negligible. [99mTc-MAS3]-SDF-1α exhibits high specificity for CXCR4 on the surface of living rat neonatal cardiomyocytes, with an affinity of 2.7 ± 0.9 nM and a Bmax of 4.8 × 104 binding sites per cell. After intravenous injection, 99mTc-labeled SDF-1α displays a blood half-life of 25.8 ± 4.6 min, rapid renal clearance with only 26.2 ± 6.1 percentage injected dose remaining in the carcass at 2 h, consistently low uptake in most organs (

Principles of nanoparticle design for overcoming biological barriers to drug delivery

Abstract: Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.

Renal clearance of quantum dots.

Abstract: The field of nanotechnology holds great promise for the diagnosis and treatment of human disease. However, the size and charge of most nanoparticles preclude their efficient clearance from the body as intact nanoparticles. Without such clearance or their biodegradation into biologically benign components, toxicity is potentially amplified and radiological imaging is hindered. Using intravenously administered quantum dots in rodents as a model system, we have precisely defined the requirements for renal filtration and urinary excretion of inorganic, metal-containing nanoparticles. Zwitterionic or neutral organic coatings prevented adsorption of serum proteins, which otherwise increased hydrodynamic diameter by >15 nm and prevented renal excretion. A final hydrodynamic diameter <5.5 nm resulted in rapid and efficient urinary excretion and elimination of quantum dots from the body. This study provides a foundation for the design and development of biologically targeted nanoparticles for biomedical applications.

Analysis of nanoparticle delivery to tumours

Abstract: This Perspective explores and explains the fundamental dogma of nanoparticle delivery to tumours and answers two central questions: ‘how many nanoparticles accumulate in a tumour?’ and ‘how does this number affect the clinical translation of nanomedicines?’

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.