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Cancer nanomedicine: from targeted delivery to combination therapy.

Xu X, Ho W, Zhang X, Bertrand N, Farokhzad O - Trends Mol Med (2015)

Bottom Line: The unique properties of nanoparticles (NPs), such as large surface-to-volume ratio, small size, the ability to encapsulate various drugs, and tunable surface chemistry, give them many advantages over their bulk counterparts.This includes multivalent surface modification with targeting ligands, efficient navigation of the complex in vivo environment, increased intracellular trafficking, and sustained release of drug payload.These advantages make NPs a mode of treatment potentially superior to conventional cancer therapies.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Nanomedicine and Biomaterials, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA. Electronic address: xiaoyang@njit.edu.

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Passive targeting, active targeting, and combinatorial deliveryIn passive targeting (left), the NPs passively extravasate though the leaky vasculature via the EPR effect and preferentially accumulate in tumors. In active targeting (middle), targeting ligands on the surface of the NP trigger receptor-mediated endocytosis for enhanced cellular uptake. In combinatorial delivery (right), two or more therapeutic agents inhibit different or identical disease pathways for a synergistic effect.
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Figure 3: Passive targeting, active targeting, and combinatorial deliveryIn passive targeting (left), the NPs passively extravasate though the leaky vasculature via the EPR effect and preferentially accumulate in tumors. In active targeting (middle), targeting ligands on the surface of the NP trigger receptor-mediated endocytosis for enhanced cellular uptake. In combinatorial delivery (right), two or more therapeutic agents inhibit different or identical disease pathways for a synergistic effect.

Mentions: A major benefit of nanomedicine is the improved biodistribution of therapeutic agents through passive targeting, a defining feature of first-generation NPs. The enhanced permeability and retention (EPR) effect refers to the fact that tumors retain more polymeric NPs, proteins, liposomes, and micelles than other tissues [10,37,38]. Most tumors have an abnormally dense and permeable vasculature created through stimulation by vascular endothelial growth factor (VEGF). Tight junctions in normal vasculature prevent particles larger than 2 nm from crossing between endothelial cells. However, the tight junctions and basement membrane of tumor vasculature are disordered, allowing entities from 10–500 nm in size to extravasate and accumulate within the tumor interstitium [39,40]. The lymphatic drainage system is also impaired in tumors, further entrapping macromolecular particles and delaying their clearance [41,42]. Passive targeting is based on both the minute size of drug carriers as well as the leaky neovasculature of the tumor (Figure 3). With the longer blood circulation brought about by “stealth” modification (e.g. PEGylation), increased accumulation of NPs is possible through the EPR effect [39].


Cancer nanomedicine: from targeted delivery to combination therapy.

Xu X, Ho W, Zhang X, Bertrand N, Farokhzad O - Trends Mol Med (2015)

Passive targeting, active targeting, and combinatorial deliveryIn passive targeting (left), the NPs passively extravasate though the leaky vasculature via the EPR effect and preferentially accumulate in tumors. In active targeting (middle), targeting ligands on the surface of the NP trigger receptor-mediated endocytosis for enhanced cellular uptake. In combinatorial delivery (right), two or more therapeutic agents inhibit different or identical disease pathways for a synergistic effect.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4385479&req=5

Figure 3: Passive targeting, active targeting, and combinatorial deliveryIn passive targeting (left), the NPs passively extravasate though the leaky vasculature via the EPR effect and preferentially accumulate in tumors. In active targeting (middle), targeting ligands on the surface of the NP trigger receptor-mediated endocytosis for enhanced cellular uptake. In combinatorial delivery (right), two or more therapeutic agents inhibit different or identical disease pathways for a synergistic effect.
Mentions: A major benefit of nanomedicine is the improved biodistribution of therapeutic agents through passive targeting, a defining feature of first-generation NPs. The enhanced permeability and retention (EPR) effect refers to the fact that tumors retain more polymeric NPs, proteins, liposomes, and micelles than other tissues [10,37,38]. Most tumors have an abnormally dense and permeable vasculature created through stimulation by vascular endothelial growth factor (VEGF). Tight junctions in normal vasculature prevent particles larger than 2 nm from crossing between endothelial cells. However, the tight junctions and basement membrane of tumor vasculature are disordered, allowing entities from 10–500 nm in size to extravasate and accumulate within the tumor interstitium [39,40]. The lymphatic drainage system is also impaired in tumors, further entrapping macromolecular particles and delaying their clearance [41,42]. Passive targeting is based on both the minute size of drug carriers as well as the leaky neovasculature of the tumor (Figure 3). With the longer blood circulation brought about by “stealth” modification (e.g. PEGylation), increased accumulation of NPs is possible through the EPR effect [39].

Bottom Line: The unique properties of nanoparticles (NPs), such as large surface-to-volume ratio, small size, the ability to encapsulate various drugs, and tunable surface chemistry, give them many advantages over their bulk counterparts.This includes multivalent surface modification with targeting ligands, efficient navigation of the complex in vivo environment, increased intracellular trafficking, and sustained release of drug payload.These advantages make NPs a mode of treatment potentially superior to conventional cancer therapies.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Nanomedicine and Biomaterials, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemical, Biological and Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, NJ 07102, USA. Electronic address: xiaoyang@njit.edu.

Show MeSH
Related in: MedlinePlus