Delivering nanomedicine to solid tumors

By Rakesh K. Jain, Triantafyllos Stylianopoulos. Nature Reviews Clinical Oncology, 2010

2,997 citations recorded by the source corpus.

Recent advances in nanotechnology have offered new hope for cancer detection, prevention, and treatment. While the enhanced permeability and retention effect has served as a key rationale for using nanoparticles to treat solid tumors, it does not enable uniform delivery of these particles to all regions of tumors in sufficient quantities. This heterogeneous distribution of therapeutics is a result of physiological barriers presented by the abnormal tumor vasculature and interstitial matrix. These barriers are likely to be responsible for the modest survival benefit offered by many FDA-approved nanotherapeutics and must be overcome for the promise of nanomedicine in patients to be realized. Here, we review these barriers to the delivery of cancer therapeutics and summarize strategies that have been developed to overcome these barriers. Finally, we discuss design considerations for optimizing the delivery of nanoparticles to tumors.

Subfields: Biomaterials, Biomedical Engineering, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e4e68dfe567519423d5fea6a9128ee1edaef77a0

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Citations in the corpus

Drug targeting to tumors: principles, pitfalls and (pre-) clinical progress. (2012, background): “Drug delivery scientists generally have an incomplete knowledge of tumor biology and of the anatomical and (patho-) physiological properties of tumors, and therefore tend to neglect the fact that the EPR effect is a highly heterogeneous phenomenon, which varies substantially from tumor model to tumo”
First-in-humans trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liver involvement. (2013, background): “Distribution to tumors with leaky microvasculature containing endothelial pores is thought to occur through the enhanced permeability and retention (EPR) mechanism described for liposomes and other nanoparticles (25, 26).”
Improving Conventional Enhanced Permeability and Retention (EPR) Effects; What Is the Appropriate Target? (2013, background): “The aggregate EPR effect is dependent on factors, (15, 16) in which tumor-specific biological features are considered to affect the heterogeneity, including 1.”
Factors controlling the pharmacokinetics, biodistribution and intratumoral penetration of nanoparticles. (2013, background): “While ligand targeted therapies are experiencing some success, an effective interaction between a ligand and the tumor cell can occur only after the targeted nanoparticles have evaded the RES clearance, extravasated into the tumor tissue and penetrated through the ECM and stroma [65, 78].”
The effect of nanoparticle size, shape, and surface chemistry on biological systems. (2012, background): “To produce long-circulating nanoparticles that can accumulate inside tumor tissues a diameter between 30 nm and 200 nm is desired (41).”
Investigating the optimal size of anticancer nanomedicine (2014, neutral): “Breast Cancer Res Treat 83(3):249–289.”