A Nanotheranostic Agent for Synergistic Antitumor Chemo/Phototherapy Prepared by Paclitaxel-Induced Self-Assembly of PEGylated Human Serum Albumin with Prolonged Circulation

The integration of different therapies to enhance the efficacy and minimize adverse reactions has become popular recently. This approach leverages the complementary mechanisms of action of different treatments, which can lead to better therapeutic outcomes and reduced side effects. Human serum albumin (HSA) exhibits excellent drug loading ability and is often used for biomimetic tumor delivery in multidrug nanocarriers. However, albumin nanocarriers are often unstable with a short plasma half-life. Therefore, a nanotheranostic agent for synergistic antitumor chemo/phototherapy was designed to improve HSA's pharmacokinetic properties, including prolonged circulation. Cys34-specifically PEGylated HSA (PEG-cys34HSA) was used as the nanocarrier, hydrophobic paclitaxel (PTX) served as the chemotherapeutic drug and self-assembly inducer of nanoparticles (NPs), and near-infrared dye indocyanine green (ICG) was utilized for phototherapy and fluorescence imaging. PEGylation with 20 kDa polyethylene glycol (PEG20kD) promoted the formation of uniform and regular NPs more effectively than PEG5kD. PEG20kD also enhanced the particle size, drug loading, and encapsulation efficiency. Moreover, PEG20kD significantly enhanced tumor targeting without hindering endocytosis, transport, and release of NPs. PEG20kD-cys34HSA/PTX/ICG-mediated combination therapy exhibited synergistic inhibitory effects on tumor growth both in vitro and in vivo. Thus, PEG20kD-cys34HSA shows potential as an alternative nanocarrier. This study provides the foundation for future investigations into PEG-modified nanocarriers and comprehensive tumor treatment.