Tissue-penetrating delivery of compounds and nanoparticles into tumors

By K. Sugahara, T. Teesalu, P. Karmali, V. R. Kotamraju, L. Agemy, O. Girard, D. Hanahan, R. Mattrey, Erkki Ruoslahti. Cancer Cell, 2009

1,099 citations recorded by the source corpus.

SUMMARY Poor penetration of drugs into tumors is a major obstacle in tumor treatment. We describe a strategy for peptide-mediated delivery of compounds deep into the tumor parenchyma that employs a tumor homing peptide, iRGD (CRGDK/RGPD/EC). Intravenously injected compounds coupled to iRGD bound to tumor vessels and spread into the extravascular tumor parenchyma, whereas conventional RGD peptides only delivered the cargo to the blood vessels. iRGD homes to tumors through a 3-step process: The RGD motif mediates binding to αv integrins on tumor endothelium, a proteolytic cleavage then exposes a binding motif for neuropilin-1, which mediates penetration into tissue and cells. Conjugation to iRGD significantly improved the sensitivity of tumor imaging agents and enhanced the activity of an anti-tumor drug.

Subfields: Biomaterials, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/4453b62a5102d3b5b4d25b6d4d3b0ea572b0a0a2

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Citations in the corpus

Advances in therapeutic applications of extracellular vesicles (2019, background): “In this case, the EV source cell was engineered to express Lamp2b fused to v integrin-specific iRGD (CRGDK/RGPD/EC) peptide, which previously had been demonstrated to have efficient tumor targeting properties when assessed in prostate, breast, cervical, and pancreatic cancer models (136).”
Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. (2014, background): “is found to be internalized by its targeted tumor cells indicating its cell-penetrating abilities [233, 269].”
Strategies in the design of nanoparticles for therapeutic applications (2010, background): “Strategies that aim to target tumour vasculature have the added benefit of the target being readily accessible to circulating nanoparticles compared to strategies that target receptors on the tumour cells themselve”
Delivering nanomedicine to solid tumors (2010, background): “The targeting of the tumor vasculature by nanoparticles armed with targeting peptides suppresses tumor growth and metastasis in mice”
A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. (2014, background): “The tumor targeting capability of exosomes was conferred by engineering the imDCs to express lysosomeassociated membrane glycoprotein 2b (Lamp2b), a well-characterized exosomal membrane protein [12], fused with iRGD (CRGDKGPDC) targeting peptide for av integrin [13].”