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Current Approaches for Improving Intratumoral Accumulation and Distribution of Nanomedicines.

Durymanov MO, Rosenkranz AA, Sobolev AS - Theranostics (2015)

Bottom Line: The ability of nanoparticles and macromolecules to passively accumulate in solid tumors and enhance therapeutic effects in comparison with conventional anticancer agents has resulted in the development of various multifunctional nanomedicines including liposomes, polymeric micelles, and magnetic nanoparticles.These "smart" systems have enabled highly effective delivery of drugs, genes, shRNA, radioisotopes, and other therapeutic molecules.However, the resulting therapeutically relevant local concentrations of anticancer agents are often insufficient to cause tumor regression and complete elimination.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Molecular Genetics of Intracellular Transport, Institute of Gene Biology, Russian Academy of Sciences, 34/5, Vavilov St., 199334, Moscow, Russia.

ABSTRACT
The ability of nanoparticles and macromolecules to passively accumulate in solid tumors and enhance therapeutic effects in comparison with conventional anticancer agents has resulted in the development of various multifunctional nanomedicines including liposomes, polymeric micelles, and magnetic nanoparticles. Further modifications of these nanoparticles have improved their characteristics in terms of tumor selectivity, circulation time in blood, enhanced uptake by cancer cells, and sensitivity to tumor microenvironment. These "smart" systems have enabled highly effective delivery of drugs, genes, shRNA, radioisotopes, and other therapeutic molecules. However, the resulting therapeutically relevant local concentrations of anticancer agents are often insufficient to cause tumor regression and complete elimination. Poor perfusion of inner regions of solid tumors as well as vascular barrier, high interstitial fluid pressure, and dense intercellular matrix are the main intratumoral barriers that impair drug delivery and impede uniform distribution of nanomedicines throughout a tumor. Here we review existing methods and approaches for improving tumoral uptake and distribution of nano-scaled therapeutic particles and macromolecules (i.e. nanomedicines). Briefly, these strategies include tuning physicochemical characteristics of nanomedicines, modulating physiological state of tumors with physical impacts or physiologically active agents, and active delivery of nanomedicines using cellular hitchhiking.

No MeSH data available.


Related in: MedlinePlus

The principle of cellular hitchhiking. Tumor-tropic cells can be loaded with nanomedicines via internalization, nonspecific surface adsorption, ligand-receptor interactions, and covalent binding. Furthermore, hitchhiked cells can be genetically engineered to impart additional capabilities to them. Injected intravenously, these cells can actively extravasate in tumor and relatively freely move in tumor interstitium.
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Figure 2: The principle of cellular hitchhiking. Tumor-tropic cells can be loaded with nanomedicines via internalization, nonspecific surface adsorption, ligand-receptor interactions, and covalent binding. Furthermore, hitchhiked cells can be genetically engineered to impart additional capabilities to them. Injected intravenously, these cells can actively extravasate in tumor and relatively freely move in tumor interstitium.

Mentions: Use of cells with tumor-homing capacity for delivery of nanomedicines is a relatively new and appealing approach in cancer therapy (Fig. 2). Being natural “moving gears” per se, these cells confer their own “active” properties to attached nanoparticles, making them capable of tumor targeting, of crossing endothelial barrier, and of penetrating to poorly perfused areas of a tumor. These cells can be isolated from bone marrow and other sources, genetically engineered to impart additional capabilities, loaded with nanoparticles, and injected intravenously back into the patient. Nanoparticles can be attached to tumor-tropic cells due to internalization, nonspecific surface adsorption, ligand-receptor interactions, and covalent binding to amine (—NH2) or thiol (—SH) groups intrinsic to cell membrane proteins, or to other reactive groups introduced exogenously into plasma membrane 133.


Current Approaches for Improving Intratumoral Accumulation and Distribution of Nanomedicines.

Durymanov MO, Rosenkranz AA, Sobolev AS - Theranostics (2015)

The principle of cellular hitchhiking. Tumor-tropic cells can be loaded with nanomedicines via internalization, nonspecific surface adsorption, ligand-receptor interactions, and covalent binding. Furthermore, hitchhiked cells can be genetically engineered to impart additional capabilities to them. Injected intravenously, these cells can actively extravasate in tumor and relatively freely move in tumor interstitium.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4493538&req=5

Figure 2: The principle of cellular hitchhiking. Tumor-tropic cells can be loaded with nanomedicines via internalization, nonspecific surface adsorption, ligand-receptor interactions, and covalent binding. Furthermore, hitchhiked cells can be genetically engineered to impart additional capabilities to them. Injected intravenously, these cells can actively extravasate in tumor and relatively freely move in tumor interstitium.
Mentions: Use of cells with tumor-homing capacity for delivery of nanomedicines is a relatively new and appealing approach in cancer therapy (Fig. 2). Being natural “moving gears” per se, these cells confer their own “active” properties to attached nanoparticles, making them capable of tumor targeting, of crossing endothelial barrier, and of penetrating to poorly perfused areas of a tumor. These cells can be isolated from bone marrow and other sources, genetically engineered to impart additional capabilities, loaded with nanoparticles, and injected intravenously back into the patient. Nanoparticles can be attached to tumor-tropic cells due to internalization, nonspecific surface adsorption, ligand-receptor interactions, and covalent binding to amine (—NH2) or thiol (—SH) groups intrinsic to cell membrane proteins, or to other reactive groups introduced exogenously into plasma membrane 133.

Bottom Line: The ability of nanoparticles and macromolecules to passively accumulate in solid tumors and enhance therapeutic effects in comparison with conventional anticancer agents has resulted in the development of various multifunctional nanomedicines including liposomes, polymeric micelles, and magnetic nanoparticles.These "smart" systems have enabled highly effective delivery of drugs, genes, shRNA, radioisotopes, and other therapeutic molecules.However, the resulting therapeutically relevant local concentrations of anticancer agents are often insufficient to cause tumor regression and complete elimination.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Molecular Genetics of Intracellular Transport, Institute of Gene Biology, Russian Academy of Sciences, 34/5, Vavilov St., 199334, Moscow, Russia.

ABSTRACT
The ability of nanoparticles and macromolecules to passively accumulate in solid tumors and enhance therapeutic effects in comparison with conventional anticancer agents has resulted in the development of various multifunctional nanomedicines including liposomes, polymeric micelles, and magnetic nanoparticles. Further modifications of these nanoparticles have improved their characteristics in terms of tumor selectivity, circulation time in blood, enhanced uptake by cancer cells, and sensitivity to tumor microenvironment. These "smart" systems have enabled highly effective delivery of drugs, genes, shRNA, radioisotopes, and other therapeutic molecules. However, the resulting therapeutically relevant local concentrations of anticancer agents are often insufficient to cause tumor regression and complete elimination. Poor perfusion of inner regions of solid tumors as well as vascular barrier, high interstitial fluid pressure, and dense intercellular matrix are the main intratumoral barriers that impair drug delivery and impede uniform distribution of nanomedicines throughout a tumor. Here we review existing methods and approaches for improving tumoral uptake and distribution of nano-scaled therapeutic particles and macromolecules (i.e. nanomedicines). Briefly, these strategies include tuning physicochemical characteristics of nanomedicines, modulating physiological state of tumors with physical impacts or physiologically active agents, and active delivery of nanomedicines using cellular hitchhiking.

No MeSH data available.


Related in: MedlinePlus