Nanogels enhance delivery of tumor-suppressing drug

The prodrug 5-aminolevulinic acid (5-ALA) has been shown to be highly effective at treating many skin diseases and cancers. In diseased cells, prodrugs — which are not themselves pharmacologically active — are metabolized into an active drug. In cancer cells, 5-ALA is transformed into protoporphyrin IX, which can be activated for photodynamic therapy. However, uptake of 5-ALA in tumor cells is limited, reducing its effectiveness and increasing side effects.

Liu et al. developed targeted nanogels to aid in 5-ALA delivery. In experiments, they demonstrated increased uptake of 5-ALA when using these nanogels.

Nanogels are often used for drug delivery due to their ability to encapsulate unstable or reactive compounds, keeping them preserved and functional for longer. To specifically target tumor cells, the authors attached folic acid ligands to the surface of their nanogels.

“Nanogels functionalized with folate ligands exploit the overexpression of folate receptors on many cancer cells, enabling precise tumor targeting and reducing off-site toxicity,” said author Rong Zhang.

The researchers performed both in vitro and in vivo tests of their method to determine its effectiveness. Their in vitro tests showed increased uptake of 5-ALA in tumor cells, along with greater stability and efficacy. In skin cancer animal models, the authors’ method demonstrated its ability to suppress tumors while minimizing toxicity in surrounding cells.

The group is excited about their results as an improvement on an existing treatment and as a proof of concept of a promising method for drug delivery.

“This work not only advances photodynamic therapy but also provides a blueprint for designing smart, tumor-microenvironment-responsive delivery systems, with implications extending beyond oncology to inflammatory or infectious diseases,” said Zhang.

Source: “Preparation of targeting nanogels for controlled delivery of 5-aminolevulinic acid triggered by matrix metalloproteinases as photodynamic therapy,” by Xiao Liu, Yuan Zhang, Peng Zhang, Kang Ge, Ruzhi Zhang, Yixin Sun, Yang Sheng, Mark Bradley, and Rong Zhang, Biointerphases (2025). The article can be accessed at https://doi.org/10.1116/6.0004203 .