Self-assembly of pentapeptides into morphology-adaptable nanomedicines for enhanced combinatorial chemo-photodynamic therapy

Cheng, ZF (Cheng, Zhifei)^{[ 1 ]} ; Cheng, YY (Cheng, Yuanyuan)^{[ 2 ]} ; Chen, Q (Chen, Qian)^{[ 2 ]} ; Li, MM (Li, Mingming)^{[ 1 ]} ; Wang, J (Wang, Jie)^{[ 3 ]} ; Liu, H (Liu, Hui)^{[ 2 ]} ; Li, MW (Li, Mengwen)^{[ 2 ]} ; Ning, YS (Ning, Yashan)^{[ 1 ]} ; Yu, ZL (Yu, Zhilin)^{[ 1 ]} ; Wang, YS (Wang, Yinsong)^{[ 2 ]} ; Wang, H (Wang, Hao)^{[ 3 ]} ...更少内容

NANO TODAY, 2020, 33, 文献号: 100878

DOI: 10.1016/j.nantod.2020.100878

摘要

The persistent morphology of conventional delivering systems limits their capability to further simultaneously optimize pharmokinetics and overcome the physiological delivering barriers. To address this challenge, here we report nanomedicines delivered by morphology-adaptable platforms for enhanced drug delivering and combinatorial chemo-photodynamic therapeutic efficacy. The nanomedicines were created by co-assembling a pentapeptide (AmpF) containing a 4-amino proline (Amp) with its two derivatives CPT-AmpF and IR820-AmpF, which are functionalized by drug camptothecin (CPT) and photo-sensitizer new indocyanine green IR820, respectively. The resulting nanomedicines formed superhelices and nanoparticles under neutral and mild acidic pH conditions. Cellular experiments revealed that the nanomedicines were up-taken by breast cancer cells via an endo-/lysosome-mediated mechanism, thus allowing the nanomedicines to undergo a reversible superhelice-nanoparticle morphological transition during the delivering pathway. Therefore, the superhelcial morphology of the nanomedicines prolonged blood circulation and tumor retention, whereas the transformed nanoparticles facilitated penetration and accumulation at tumor sites. Compared to the morphology-persistent counterparts, the improved delivering efficiency of the adaptable nanomedicines resulted in the enhanced combinatorial chemophotodynamic therapy against breast tumors, thus potentially leading to a facile and versatile strategy for drug delivery and paving the way toward new-generation nanomedicines in the future. (C) 2020 Elsevier Ltd. All rights reserved.