Binding and internalization in receptor-targeted carriers. The complex role of CD44 in the uptake of hyaluronic acid-based nanoparticles (siRNA delivery)

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • Julio Manuel Rios De La Rosa
  • Ponpawee Pingrajai
  • Maria Pelliccia
  • Enrique Lallana-Ozores
  • Arianna Gennari
  • Walter Rocchia

Abstract

This paper is about the actual role of CD44 in the perspective of a hyaluronic acid (HA)-based, targeted therapy. CD44 is the main HA receptor: it is present both in healthy and cancerous cells, but is overexpressed in many carcinomas, with important roles in their initiation and malignancy. This, and its endocytic capacities, have encouraged the use of HA to design CD44-targeting carriers.
Here, we have used HA-decorated nanoparticles to deliver a siRNA payload to a panel of human cells comprising both tumoral (AsPC-1, PANC-1, HT-29, HCT-116) and non-tumoral (fibroblasts, differently polarized THP-1 macrophages, HUVEC) lines; we have evaluated in a comparative and quantitative fashion the initial binding of the nanoparticles, their internalization rate and the eventual silencing efficiency (cyclophilin B (PPIB) gene).
A first result of our study is that, in general, tumoral cells internalized faster and experienced higher silencing than non-tumoral cells. This result is promising as it suggests that, when in a tumor environment, HA nanocarriers may have limited off-target effects.
A more far-reaching result comes from the quantitative analysis of the inter-relation between the four parameters of our study (i.e. total CD44 expression, extent of HA cell surface binding, internalization rate and silencing efficiency). Our experiments showed no correlation between extent of binding (an early event) and any of the other parameters. On the contrary, silencing correlated well both with the speed of the internalization process and also with CD44 expression. This study, therefore, confirms on one hand that HA-based carriers can perform a targeted therapeutic action, but on the other it suggests that this may not be due to the selective binding of a cell surface marker, but possibly to a later recognition event leading to selective internalization.

Bibliographical metadata

Original languageEnglish
Article number1901182
JournalAdvanced Healthcare Materials
Volume8
Issue number24
Early online date18 Nov 2019
DOIs
Publication statusPublished - 18 Dec 2019

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