# Tailoring the Composition of HA/PEG Mixed Nano-Assemblies for Anticancer Drug Delivery

## TL;DR

This study explores how adjusting the composition of HA/PEG nano-assemblies can improve targeted drug delivery for cancer treatment.

## Contribution

The work introduces a method to fine-tune nano-assembly properties for enhanced cancer cell targeting and drug delivery.

## Key findings

- Nano-assemblies with higher HA content showed increased internalization by cancer cells.
- All formulations had high encapsulation efficiency and stability during storage.
- Cytotoxicity was enhanced with higher HA content, demonstrating tunable therapeutic effects.

## Abstract

Self-assembling amphiphilic polymers represent highly promising materials with emerging applications across various fields. In these polymers, the presence of hydrophilic and hydrophobic segments within their structure drives the self-assembly process in aqueous environments, leading to organized structures capable of incorporating lipophilic drugs. Their high chemical versatility enables the design of tailored structures to meet specific requirements, such as the active targeting ability, thereby broadening their potential applications. In this work, a polyethylene glycol-phospholipid conjugate was employed to form nanocarriers loaded with a lipophilic derivative of gemcitabine. To achieve nano-assemblies actively targeted towards cancer cells overexpressing the hyaluronic acid (HA) receptor CD44, a HA-phospholipid conjugate was co-formulated in various molar ratios (1%, 10%, and 20%). All formulations exhibited a mean diameter below 130 nm, a negative zeta potential (approximately −30 mV), and a high encapsulation efficiency (above 90%). These nano-assemblies demonstrated stability during storage and effectively released the encapsulated drug in a cell culture medium. Upon incubation with cancer cells, the nano-assemblies were internalized via a CD44 endocytosis-mediated mechanism, with the extent of internalization depending on the HA conjugate content. Consistently, cell viability studies revealed that the nanocarriers decorated with higher amounts of HA exerted a higher cytotoxicity, enabling a fine tuning of the nano-assembly properties.