Flexible Hollow Human Serum Albumin-Catalase Nanocapsules with High Accumulation and Uptake Ability for Enhanced Photodynamic Therapy

Yuyuan Shi,1,* Ying Zhao,2,* Wen Kang,2 Wei Lu,3 Dong Chen,3 Jun Tao,3 Jing Li,3 Ruifa Yu,3 Jiajia Zhao,3 Rui Tang,3 Zhaogang Teng,3 Lixing Weng1 1College of Geography and Biological Information, Nanjing University of Posts and Telecommunications, Nanjing, People’s Republic of China; 2Department of Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 3Key Laboratory for Organic Electronics & Information Displays and Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials, Jiangsu National Synergetic Innovation Centre for Advanced Materials, Nanjing University of Posts and Telecommunications, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhaogang Teng; Lixing Weng, Email iamzgteng@njupt.edu.cn; lxweng@njupt.edu.cnIntroduction: Photodynamic therapy (PDT) has attracted increasing attention for tumor treatment because of its minimal invasiveness and specific spatiotemporal selectivity. However, insufficient tumor accumulation and low cellular uptake of photosensitizers limit its therapeutic efficacy.Methods: In this study, flexible hollow human serum albumin/catalase nanocapsules (HSA/CATs) were created using a core-assisted protein-coating method and combined with the photosensitizer chlorin e6 (HSA/CAT@Ce6) for PDT.Results and Discussion: Transmission electron microscopy (TEM) images demonstrate that HSA/CAT nanocapsules are flexible, with a uniform diameter (310 nm) and a well-defined hollow structure. Thanks to their flexibility, HSA/CAT@Ce6 nanocapsules show a higher cellular uptake than rigid nanoparticles. The nanocapsules effectively generate reactive oxygen species (ROS) in 4T1 cells because of their high cellular uptake and catalytic capacity, remarkably enhancing their in vitro PDT efficacy. In addition, the in vivo tumor accumulation of HSA/CAT@Ce6 nanocapsules is significantly larger than that of rigid nanoparticles and Ce6, meaning they are highly effective in tumor cell ablation. This demonstrates that our flexible nanoplatform holds great promise for enhancing PDT of tumor.Keywords: flexible nanoplatform, human serum albumin, sufficient tumor accumulation, high cellular uptake, photodynamic therapy