# Coumarin‐Caged Nanoparticle for Light‐Driven Surface Modification

## TL;DR

This paper introduces light-responsive nanoparticles that can control cell uptake by modifying their surface properties using a coumarin-based protecting group.

## Contribution

The novel use of coumarin-derived PPG to dynamically control NP surface charge and cell uptake via light exposure.

## Key findings

- Attaching PPG to CPP reduces the NP surface charge and decreases cell uptake.
- Light irradiation cleaves PPG, restoring surface charge and increasing cell uptake.
- This method offers potential for targeted drug delivery in biological environments.

## Abstract

Photo‐labile protecting groups (PPG) allow for the selective activation of an originally caged moiety by light exposure at a specific wavelength. Incorporation of PPG in nanoparticles (NPs) enables precise spatiotemporal control over NPs surface properties. Thus, physicochemical and biological properties of NPs can be modified even after administration in a biological environment. In this study, this mechanism is used to control the cell uptake of NPs. To this end, polymeric core–shell NPs are used composed of poly(D, L‐lactide‐co‐glycolide) and a poly(ethylene glycol)‐b‐poly(D, L‐lactide) block copolymer, modified with positively charged cell‐penetrating peptide (CPP). Surface charge of CPP‐NPs (+23.50 mV), measured as zetapotential, is effectively diminished by the attachment of coumarin‐derived PPG to CPP (+12.50 mV), resulting in reduced cell uptake. Upon light irradiation with light‐emitting diode (λ = 365 nm) the PPG is cleaved, restoring the zetapotential (+24.67 mV) and triggering an enhanced cell uptake. This opens the door to trigger the cellular uptake of NPs that are intended to transport drugs to their target cells in the future.

Photo‐responsive nanoparticles (NPs) enable spatiotemporal control over drug delivery. Attachment of a photo‐labile protecting group (PPG) to cell‐penetrating peptide (CPP) effectively camouflages the positive charge of NPs. Light irradiation cleaves the PPG, exposing the CPP on the NP surface and thereby enhancing cellular uptake.© 2025 WILEY‐VCH GmbH