Preparation of targeting nanogels for controlled delivery of 5-aminolevulinic acid triggered by matrix metalloproteinases as photodynamic therapy.

5-Aminolevulinic acid (5-ALA) is a prodrug of the photodynamic therapy (PDT) for the treatment of certain skin diseases and neuronal cancers in the clinic. However, it is difficult for 5-ALA to target specific cells and, therefore, to accumulate within deeper lesions, leading to poor conversion of protoporphyrin IX, the active photodynamic agent. To solve this problem, targeted nanogels were developed for controlled 5-ALA delivery. Here, nanogels with folic acid as a targeting ligand were prepared by inverse microemulsion polymerization using the peptide cross-linker acryl-PLGLAGK(Alloc)-NH2, a generic substrate for matrix metalloproteinases, enzymes associated with many tumors. The stability, entrapment efficiency, drug loading, and drug release ability of the nanogels were studied with skin cancer cells (A2058) and showed that the targeting nanogels enhanced the concentration of 5-ALA in tumor cells and improved the efficiency of PDT in vitro. In vivo experiments showed that the targeting nanogels loaded with 5-ALA dramatically inhibited the development of skin cancer.