@article{Qu2023, 
author = {Haijing Qu and Han Chen and Wei Cheng and Yuqing Pan and Zhiran Duan and Yanjun Wang and Xing-Jie Liang and Xiangdong Xue},
title = {Charge-reversible crosslinked nanoparticle for pro-apoptotic peptide delivery and synergistic photodynamic cancer therapy},
year = {2023},
journal = {Nano Research},
volume = {16},
number = {12},
pages = {13267-13282},
keywords = {photodynamic therapy, peptide delivery, charge-reversible nanoparticle, crosslinked nanoparticle, synergistic cancer treatment},
url = {https://www.sciopen.com/article/10.1007/s12274-023-5912-7},
doi = {10.1007/s12274-023-5912-7},
abstract = {Although anti-cancer nanotherapeutics have made breakthroughs, many remain clinically unsatisfactory due to limited delivery efficiency and complicated biological barriers. Here, we prepared charge-reversible crosslinked nanoparticles (PDC NPs) by supramolecular self-assembly of pro-apoptotic peptides and photosensitizers, followed by crosslinking the self-assemblies with polyethylene glycol to impart tumor microenvironment responsiveness and charge-reversibility. The resultant PDC NPs have a high drug loading of 68.3%, substantially exceeding that of 10%–15% in conventional drug delivery systems. PDC NPs can overcome the delivery hurdles to significantly improve the tumor accumulation and endocytosis of payloads by surface charge reversal and responsive crosslinking strategy. Pro-apoptotic peptides target the mitochondrial membranes and block the respiratory effect to reduce local oxygen consumption, which extensively augments oxygen-dependent photodynamic therapy (PDT). The photosensitizers around mitochondria increased along with the peptides, allowing PDT to work with pro-apoptotic peptides synergistically to induce tumor cell death by mitochondria-dependent apoptotic pathways. Our strategy would provide a valuable reference for improving the delivery efficiency of hydrophilic peptides and developing mitochondrial-targeting cancer therapies.}
}