# Surface Density of Mono- and Trivalent High-Mannan-Derived Targeting Structures with Different Affinities Impacts Cellular Uptake of Human Serum Albumin-Derived Nanocarriers

## TL;DR

This study examines how the type and density of targeting structures on nanocarriers affect their uptake by immune cells, offering insights into improving drug delivery.

## Contribution

The study introduces a method to control the valency and surface density of targeting structures on nanocarriers for immune cell targeting.

## Key findings

- Monovalent and trivalent targeting structures were synthesized and tested for their affinity to immune cell receptors.
- Surface modification of nanocarriers influenced cellular uptake and selectivity in immune cell populations.
- Low valency and saturated nanocarriers showed well-defined mannose epitope counts for targeted delivery.

## Abstract

Actively targeted
delivery of nanocarriers (NC) modified with targeting
structures (TS) binding to cell surface receptors, specific to target
cells, enables enhanced selectivity and efficacy of cellular uptake.
This is influenced by the ligand density on the NC surface. Herein,
the impact of type, valency, and surface density of high-mannan derived
TS on the C-type lectin receptor (CLR)-mediated uptake of human serum
albumin (HSA)-based NCs in immune cell populations was investigated.
Monovalent and trivalent TSs were prepared via efficient synthesis
protocols and investigated regarding their affinity versus isolated
carbohydrate recognition domains (CRD) of CD206 and CD209 within a
NanoDSF study. Conjugation to HSA resulted in low valency and saturated
NCs with a well-defined mannose epitope count. An in vitro study with bone-marrow-derived dendritic cells and splenic immune
cells revealed the impact of the NC surface modification on cellular
uptake and cell selectivity, allowing insights into the design of
TSs and NCs.