Synthesis and characterization of bioreducible heparin-polyethyleneimine nanogels: Application as imaging-guided photosensitizer delivery vehicle in photodynamic therapy

Herein, we synthesized and characterized novel bioreducible heparin polyethyleneimine (HPC) nanogels consisting of heparin, branched polyethyleneimine (PEI) and l-cysteine. ¹H-NMR and FTIR analysis confirmed the formation of HPC nanogels while TEM and dynamic light scattering revealed uniform spherical nanoparticles with average diameter of <200 nm. Zinc phthalocyanine (ZnPC) was encapsulated via the dialysis method and the drug is released in vitro from disulfide-containing HPC nanogels in a redox-sensitive manner at low pH. Additionally, HPC nanogels possess bright blue fluorescence which eliminates the use of additional probing agent in image-guided drug delivery. Moreover, singlet oxygen detection revealed that nanogels prevented ZnPc aggregation thus enhancing ¹O₂ generation and photodynamic therapy (PDT) efficacy. These results showed that disulfide crosslinked HPC nanogels are promising vehicles for stimulated photosensitizer delivery in advanced PDT.