Poly(Glutamic Acid)-Engineered Nanoplatforms for Enhanced Cancer Phototherapy

Phototherapies, including photothermal therapy and photodynamic therapy, have gained booming development over the past several decades for their attractive non-invasiveness nature, negligible adverse effects, minimal systemic toxicity, and high spatial selectivity. Phototherapy usually requires three components: light irradiation, photosensitizers, and molecular oxygen. Photosensitizers can convert light energy into heat or reactive oxygen species, which can be used in the tumor-killing process. The direct application of photosensitizers in tumor therapy is restricted by their poor water solubility, fast clearance, severe toxicity, and low cellular uptake. The encapsulation of photosensitizers into nanostructures is an attractive strategy to overcome these critical limitations. Poly(glutamic acid) (PGA) is a kind of poly(amino acid)s containing the repeating units of glutamic acid. PGA has superiority for cancer treatment because of its good biocompatibility, low immunogenicity, and modulated pH responsiveness. The hydrophilicity nature of PGA allows the physical entrapment of photosensitizers and anticancer drugs via the construction of amphiphilic polymers. Moreover, the pendent carboxyl groups of PGA enable chemical conjugation with therapeutic agents. In this mini-review, we highlight the stateof- the-art design and fabrication of PGA-based nanoplatforms for phototherapy. We also discuss the potential challenges and future perspectives of phototherapy, and clinical translation of PGA-based nanomedicines.