Tumor microenvironment responsive PEGylated heparin pyropheophorbide a nanoconjugates for photodynamic therapy.
To deliver photosensitizers with PEGylated heparin (HP) into tumor cells for photodynamic therapy, we prepared two polyethylene glycol (PEG) functionalized HP based polymers conjugated with pyropheophorbide a (Ppa) a non GSH responsive nanoagent (HP Ppa mPEG) with the mPEG moiety chemically attached to HP directly; and a GSH responsive nanoagent (HP Ppa SS mPEG) with the mPEG moiety conjugated to HP via a disulfide linkage. The Ppa functionalized HP without PEGylation (HP Ppa) was designed as another control. These amphiphilic polymers could aggregate into nanoparticles. Cellular uptake of three nanoparticles by 4T1 cells led to abundant production of reactive oxygen species after irradiation by a 660 nm laser, inducing cell apoptosis. HP Ppa SS mPEG was found to achieve the highest tumor accumulation, the longest retention time and the best penetration into tumor tissues, resulting in the highest in vivo anticancer efficacy with 94.3 tumor growth inhibition rate, suggesting that tumor microenvironment responsive PEGylated HP based nanomedicines may act as efficient anticancer agents.
Carbohydrate polymers