Access granted: iRGD helps silicasome-encased drugs breach the tumor barrier

Abstract

In this issue of the JCI, Liu et al. use irinotecan-loaded nanoparticles to treat pancreatic adenocarcinomas in mice. Encapsulating drugs into nanoparticles has distinct advantages: it can improve the pharmacokinetics of the drug, enhance efficacy, and reduce unwanted side effects. A drawback is that the large size of nanoparticles restricts their access to the tumor interior. Liu and colleagues show that the cyclic tumor-penetrating peptide iRGD, reported to be capable of enhancing tumor penetration by drugs, can overcome this limitation to a substantial degree when administered together with the nanoparticles. Pancreatic adenocarcinoma is a challenging malignancy to treat and in desperate need for improved treatments; therefore, advances like this are most welcome.

The Use of Alternative Strategies for Enhanced Nanoparticle Delivery to Solid Tumors

“…Cargo is delivered directly to the target tumor. Reproduced with permission from ref ( 197 ). Copyright 2017 American Society for Clinical Investigation.…”

“… 199 Similar delivery and therapeutic efficiencies have been observed for combinations of iRGD with inorganic NMs, including legumain responsive aggregable gold NPs. 197 …”

Targeted drug delivery using iRGD peptide for solid cancer treatment

“…2. 17,19,25–27 The peptide contains two critical sequence motifs, namely an integrin-binding RGD motif and neuropilin-1 (NRP-1) binding motif. The RGD motif mediates the first binding of iRGD to α v β 3 or α v β 5 integrins, which are preferentially overexpressed on tumor blood vessels endothelial cells and tumor cells.…”

Exposed CendR Domain in Homing Peptide Yields Skin-Targeted Therapeutic in Epidermolysis Bullosa

“…[5][6][7][8] The CendR sequence binds to neuropilin-1 (NRP-1), activating an extravasation and tissue penetration pathway that delivers the peptide along with its payload into the parenchyma of the tumor tissue. 3,5,8 As NRP-1 is expressed by the endothelial cells in all tissues, 3 peptides containing cryptic CendR owe their target selectivity to a combination of binding to primary receptor with a tumor-specific expression pattern, and to a proteolytic activation to expose the CendR sequence in the target organ. [5][6][7][8] Being the largest organ of the human body, skin presents unique challenges for efficient drug delivery.…”

“…3,5,8 As NRP-1 is expressed by the endothelial cells in all tissues, 3 peptides containing cryptic CendR owe their target selectivity to a combination of binding to primary receptor with a tumor-specific expression pattern, and to a proteolytic activation to expose the CendR sequence in the target organ. [5][6][7][8] Being the largest organ of the human body, skin presents unique challenges for efficient drug delivery. The primary challenge related to local, i.e., transdermal, drug delivery is the poor penetration of macromolecules into the skin.…”