Effect of ligand density, receptor density, and nanoparticle size on cell targeting.
01 Feb 2013-Nanomedicine: Nanotechnology, Biology and Medicine (Elsevier)-Vol. 9, Iss: 2, pp 194-201
TL;DR: The authors of this study investigated optimal ligand density with SPIO-based labeling and concluded that intermediate density appears to have the most optimal labeling properties from the standpoint of its T2* shortening effect.
About: This article is published in Nanomedicine: Nanotechnology, Biology and Medicine.The article was published on 2013-02-01 and is currently open access. It has received 292 citations till now. The article focuses on the topics: Ligand.
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TL;DR: The fundamental concepts of enhanced permeability and retention effect (EPR) are revisited and the mechanisms proposed to enhance preferential "retention" in the tumor, whether using active targeting of nanoparticles, binding of drugs to their tumoral targets or the presence of tumor associated macrophages are explored.
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Cites background from "Effect of ligand density, receptor ..."
...In some cases, the cooperative effect of the ligand can saturate and further increases in ligand density can have deleterious effects on cell binding [197, 198]....
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TL;DR: This review is a comprehensive description of the past decade of research into understanding how the geometry and size of nanoparticles affect their interaction with biological systems: from single cells to whole organisms.
Abstract: This review is a comprehensive description of the past decade of research into understanding how the geometry and size of nanoparticles affect their interaction with biological systems: from single cells to whole organisms. Recently, there has been a great deal of effort to use both the shape and the size of nanoparticles to target specific cellular uptake mechanisms, biodistribution patterns, and pharmacokinetics. While the successes of spherical lipid-based nanoparticles have heralded marked changes in chemotherapy worldwide, the history of asbestos-induced lung disease casts a long shadow over fibrous materials to date. The impact of particle morphology is known to be intertwined with many physicochemical parameters, namely, size, elasticity, surface chemistry, and biopersistence. In this review, we first highlight some of the morphologies observed in nature as well as shapes available to us through synthetic strategies. Following this we discuss attempts to understand the cellular uptake of nanopartic...
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References
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Abstract: Nanostructures of different sizes, shapes and material properties have many applications in biomedical imaging, clinical diagnostics and therapeutics1,2,3,4,5,6. In spite of what has been achieved so far, a complete understanding of how cells interact with nanostructures of well-defined sizes, at the molecular level, remains poorly understood. Here we show that gold and silver nanoparticles coated with antibodies can regulate the process of membrane receptor internalization. The binding and activation of membrane receptors and subsequent protein expression strongly depend on nanoparticle size. Although all nanoparticles within the 2–100 nm size range were found to alter signalling processes essential for basic cell functions (including cell death)7, 40- and 50-nm nanoparticles demonstrated the greatest effect. These results show that nanoparticles should no longer be viewed as simple carriers for biomedical applications, but can also play an active role in mediating biological effects. The findings presented here may assist in the design of nanoscale delivery and therapeutic systems and provide insights into nanotoxicity.
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TL;DR: A cell labeling approach using short HIV-Tat peptides to derivatize superparamagnetic nanoparticles is developed, which efficiently internalized into hematopoietic and neural progenitor cells in quantities up to 10–30 pg of super paramagnetic iron per cell.
Abstract: The ability to track the distribution and differentiation of progenitor and stem cells by high-resolution in vivo imaging techniques would have significant clinical and research implications We have developed a cell labeling approach using short HIV-Tat peptides to derivatize superparamagnetic nanoparticles The particles are efficiently internalized into hematopoietic and neural progenitor cells in quantities up to 10-30 pg of superparamagnetic iron per cell Iron incorporation did not affect cell viability, differentiation, or proliferation of CD34+ cells Following intravenous injection into immunodeficient mice, 4% of magnetically CD34+ cells homed to bone marrow per gram of tissue, and single cells could be detected by magnetic resonance (MR) imaging in tissue samples In addition, magnetically labeled cells that had homed to bone marrow could be recovered by magnetic separation columns Localization and retrieval of cell populations in vivo enable detailed analysis of specific stem cell and organ interactions critical for advancing the therapeutic use of stem cells
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Abstract: There has been progressively heightened interest in the development of targeted nanoparticles (NPs) for differential delivery and controlled release of drugs. Despite nearly three decades of research, approaches to reproducibly formulate targeted NPs with the optimal biophysicochemical properties have remained elusive. A central challenge has been defining the optimal interplay of parameters that confer molecular targeting, immune evasion, and drug release to overcome the physiological barriers in vivo. Here, we report a strategy for narrowly changing the biophysicochemical properties of NPs in a reproducible manner, thereby enabling systematic screening of optimally formulated drug-encapsulated targeted NPs. NPs were formulated by the self-assembly of an amphiphilic triblock copolymer composed of end-to-end linkage of poly(lactic-co-glycolic-acid) (PLGA), polyethyleneglycol (PEG), and the A10 aptamer (Apt), which binds to the prostate-specific membrane antigen (PSMA) on the surface of prostate cancer (PCa) cells, enabling, respectively, controlled drug release, "stealth" properties for immune evasion, and cell-specific targeting. Fine-tuning of NP size and drug release kinetics was further accomplished by controlling the copolymer composition. By using distinct ratios of PLGA-b-PEG-b-Apt triblock copolymer with PLGA-b-PEG diblock copolymer lacking the A10 Apt, we developed a series of targeted NPs with increasing Apt densities that inversely affected the amount of PEG exposure on NP surface and identified the narrow range of Apt density when the NPs were maximally targeted and maximally stealth, resulting in most efficient PCa cell uptake in vitro and in vivo. This approach may contribute to further development of targeted NPs as highly selective and effective therapeutic modalities.
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