Hydrophilic Poly(glutamic acid)-Based Nanodrug Delivery System: Structural Influence and Antitumor Efficacy

Poly(amino acids) have advanced characteristics, including unique secondary structure, enzyme degradability, good biocompatibility, and stimuli responsibility, and are suitable as drug delivery nanocarriers for tumor therapy. The isoform structure of poly(amino acids) plays an important role in their antitumor efficacy and should be researched in detail. In this study, two kinds of pH-sensitive isoforms, including α-poly(glutamic acid) (α-PGA) and γ-PGA, were selected and used as nanocarriers to prepare a nanodrug delivery system. According to the preparation results, α-PGA can be used as an ideal drug carrier. Selecting doxorubicin (DOX) as the model drug, an α-PGA/DOX nanoparticle (α-PGA/DOX NPs) with a particle size of 110.4 nm was prepared, and the drug-loading content was 66.2%. α-PGA/DOX NPs presented obvious sustained and pH-dependent release characteristics. The IC₅₀ value of α-PGA/DOX NPs was 1.06 ± 0.77 μg mL^-1, decreasing by approximately 8.5 fold in vitro against 4T1 cells after incubation for 48 h. Moreover, α-PGA/DOX NPs enhanced antitumor efficacy in vivo, the tumor inhibition rate was 67.4%, increasing 1.5 fold over DOX injection. α-PGA/DOX NPs also reduced the systemic toxicity and cardiotoxicity of DOX. In sum, α-PGA is a biosafe nanodrug delivery carrier with potential clinical application prospects.