Homing systemically administered nanoparticles to tumors relies on either passive targeting via the enhanced permeability and retention effect of leaky tumor vasculature or active targeting via decoration of the nanoparticle with tumor-specific biomolecules that facilitate tumor accumulation. In both strategies, the journey undertaken by the nanoparticle is treacherous and riddled with obstacles.
First, as soon as a nanoparticle is administered into the bloodstream the extraneous ‘foreign’ nanoparticle is tagged with opsonins that form a protein corona around the particle, flagging it for complement activation, engulfment by circulating macrophages, and rapid clearance from circulation. Second, upon encountering resident macrophages in the liver and spleen, the nanoparticle is again efficiently eliminated from the circulation by phagocytosis. Third, the nanoparticle may ride within the center of the advancing laminar flow column of blood within the vasculature such that it does not contact the endothelial lining of tumor neovasculature to facilitate tumbling through the wide interendothelial fenestrations and pores that are the hallmark of leaky chaotic immature neoangiogenic blood vessels, the enablers of the EPR effect. Fourth, upon extravasating from the tumor vasculature, the nanoparticle faces a harsh tumor microenvironment that is not conducive to interactions with cancer cells, especially the most therapy-resistant cells that thrive in a hostile hypoxic microenvironment. Not surprisingly, an appraisal of published reports of nanoparticle delivery to tumors concluded that on average only 0.7% of intravenously administered nanoparticles reach the tumor as a consequence of these pharmacokinetic impediments. Yet, nanoparticles have shown promise in terms of minimizing systemic exposure to drugs and thus reducing the toxicity of some chemotherapeutic agents.
Clearly, newer techniques are needed to improve tumor-specific delivery of nanoparticles to tumors and to subcellular compartments where they exert their therapeutic effects. This Research Topic will outline ongoing strategies to overcome, not just one, but as many impediments to tumor access as possible.
We welcome submissions of original research, brief communications, reviews, and mini-review articles that focus on nanoparticle transport to tumors. Topics of particular interest include, but are not limited to, the following:
- stealth coatings that reduce protein corona formation, evade opsonization, and reticuloendothelial system (RES) capture
- mechanisms involved in RES capture
- drivers and modulators of RES capture – size, shape, charge, surface chemistry, elasticity, etc
- new technology and/or methods applicable to the design, development, and analysis of extravasation
- studies of biological and/or pathophysiological variables that influence extravasation
- design, development, and analysis of stimulus-responsive nanoparticles
- design, development, and analysis of biologically inspired nanostructures that overcome physiological barriers
- studies of biological and/or pathophysiological consequences of tumor microenvironment interactions with nanoparticles (especially, stromal mesenchymal cells, endothelial cells, and immune cells)
Keywords:
nanoparticles, drug delivery, barriers, cancer, enhanced permeability, nanomaterial delivery, tumor targets
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
Homing systemically administered nanoparticles to tumors relies on either passive targeting via the enhanced permeability and retention effect of leaky tumor vasculature or active targeting via decoration of the nanoparticle with tumor-specific biomolecules that facilitate tumor accumulation. In both strategies, the journey undertaken by the nanoparticle is treacherous and riddled with obstacles.
First, as soon as a nanoparticle is administered into the bloodstream the extraneous ‘foreign’ nanoparticle is tagged with opsonins that form a protein corona around the particle, flagging it for complement activation, engulfment by circulating macrophages, and rapid clearance from circulation. Second, upon encountering resident macrophages in the liver and spleen, the nanoparticle is again efficiently eliminated from the circulation by phagocytosis. Third, the nanoparticle may ride within the center of the advancing laminar flow column of blood within the vasculature such that it does not contact the endothelial lining of tumor neovasculature to facilitate tumbling through the wide interendothelial fenestrations and pores that are the hallmark of leaky chaotic immature neoangiogenic blood vessels, the enablers of the EPR effect. Fourth, upon extravasating from the tumor vasculature, the nanoparticle faces a harsh tumor microenvironment that is not conducive to interactions with cancer cells, especially the most therapy-resistant cells that thrive in a hostile hypoxic microenvironment. Not surprisingly, an appraisal of published reports of nanoparticle delivery to tumors concluded that on average only 0.7% of intravenously administered nanoparticles reach the tumor as a consequence of these pharmacokinetic impediments. Yet, nanoparticles have shown promise in terms of minimizing systemic exposure to drugs and thus reducing the toxicity of some chemotherapeutic agents.
Clearly, newer techniques are needed to improve tumor-specific delivery of nanoparticles to tumors and to subcellular compartments where they exert their therapeutic effects. This Research Topic will outline ongoing strategies to overcome, not just one, but as many impediments to tumor access as possible.
We welcome submissions of original research, brief communications, reviews, and mini-review articles that focus on nanoparticle transport to tumors. Topics of particular interest include, but are not limited to, the following:
- stealth coatings that reduce protein corona formation, evade opsonization, and reticuloendothelial system (RES) capture
- mechanisms involved in RES capture
- drivers and modulators of RES capture – size, shape, charge, surface chemistry, elasticity, etc
- new technology and/or methods applicable to the design, development, and analysis of extravasation
- studies of biological and/or pathophysiological variables that influence extravasation
- design, development, and analysis of stimulus-responsive nanoparticles
- design, development, and analysis of biologically inspired nanostructures that overcome physiological barriers
- studies of biological and/or pathophysiological consequences of tumor microenvironment interactions with nanoparticles (especially, stromal mesenchymal cells, endothelial cells, and immune cells)
Keywords:
nanoparticles, drug delivery, barriers, cancer, enhanced permeability, nanomaterial delivery, tumor targets
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.