Materials* (MDPI; inferred from format)2018ReviewDrug Delivery
Not Fully Listed In The Supplied File; Corresponding Authors Are P.Z. ([email protected]) And S.L. ([email protected])
Conventional micro/nanoparticle synthesis techniques (e.g., emulsion, sol–gel) can produce only a limited number of shapes—mainly spherical or rod-like—and provide poor control over size, cargo loading, and surface properties. These features critically affect particle–cell interactions and in vivo biodistribution, so advanced manufacturing techniques are needed to generate well-defined micro/nanoparticles for improved therapeutic delivery. --- - Size-dependent uptake: 100 nm particles showed 2.5-fold greater uptake by Caco-2 cells than 1 µm particles and 6-fold higher uptake than 10 µm particles. - Size-dependent internalization mechanisms: Particles >500 nm are internalized mainly by phagocytosis; <500 nm by pinocytosis. Particles <200 nm enter via clathrin-coated pits; ~500 nm via caveolae-mediated internalization. ~200 nm particles are more easily routed to lysosomes than ~500 nm particles. - In vivo size effects: >200 nm particles a
Read the article →Chemical Society Reviews2017ReviewNon-viral Gene Delivery
Shahed Behzadi, Vahid Serpooshan, Wei Tao, Majd A. Hamaly, Mahmoud Y. Alkawareek, Erik C. Dreaden, Dennis Brown, Alaaldin M. Alkilany, Omid C. Farokhzad, Morteza Mahmoudi
Nanoparticles (NPs) are increasingly used in consumer goods, electronics, and pharmaceuticals, but their beneficial and/or deleterious effects ultimately arise from interactions at the cellular and subcellular level. While many NPs require safe entry into cells for therapeutic efficacy, efficient and controlled entry/trafficking remains a major challenge. A comprehensive understanding of NP cellular uptake and trafficking mechanisms is critical for designing efficient and safe nanomedicines. --- - Size: ~50 nm is the optimum size for highest cellular uptake in certain cells; larger particles (1000–2000 nm) show maximal phagocytic uptake; smaller NPs (2.1 nm) can enter the nucleus/nucleoli, while 4.4 nm NPs show reduced penetration. - Shape: Spherical NPs undergo higher cellular uptake than rod-shaped NPs; lower aspect ratio rods are taken up faster than higher aspect ratio rods; rod and disc NPs are taken up twice as quickly as spheres
Read the article →Cold Spring Harbor Perspectives in Biology2014ReviewNon-viral Gene Delivery
Satyajit Mayor, Robert G. Parton, Julie G. Donaldson
Clathrin-mediated endocytosis (CME) has long been the dominant paradigm for cellular uptake, but many endocytic pathways operate without clathrin. These clathrin-independent endocytic (CIE) pathways are increasingly recognized as distinct routes with different cargo selectivity, molecular machinery, kinetics, and intracellular destinations. The review addresses the need to organize and understand this diversity, especially for small-scale CIE processes that operate without clathrin coats and, in some cases, without dynamin. --- - Caveolae are dynamic endocytic carriers: In interphase cells, ~85% of caveolae were internalized within a 10-min observation period, with lifetimes ranging from <2 s (30% of caveolae) to >7 min. Budded structures were cavin-positive, and dynamin dependence was confirmed. - EHD2 is a negative regulator of caveolar endocytosis: Knockdown of EHD2 increases caveolar budding. EHD2 links caveolae to actin and associa
Read the article →Trends in Immunology2002ReviewNon-viral Gene Delivery
James Harris, Dirk Werling, Jayne C. Hope, Geraldine Taylor, Chris J. Howard
Caveolae and caveolin are cholesterol-rich membrane microdomains involved in endocytosis, cholesterol regulation, and signal transduction, but their presence and function in immune cells have been contentious. This review addresses the need to clarify the distribution and roles of caveolae/caveolin in mammalian immune cells, especially given emerging evidence that they mediate pathogen internalization by antigen-presenting cells and participate in immune-cell signaling. --- 1. Distribution is contentious and context-dependent: Caveolae/caveolin are commonly found in myeloid cells (macrophages, mast cells, dendritic cells, neutrophils) but not consistently in lymphoid cells. More recent evidence suggests they may be present in all immune cell types, with expression/distribution dependent on activation and/or maturation state. 2. Species and cell-type differences in caveolin localization: Human CD26+ and CD21+ peripheral blood lymphocytes
Read the article →