Self-assembly of pentapeptides into morphology-adaptable nanomedicines for enhanced combinatorial chemo-photodynamic therapy. (August 2020)

• Record Type: Journal Article
• Authors: Cheng, Zhifei; Cheng, Yuanyuan; Chen, Qian; Li, Mingming; Wang, Jie; Liu, Hui; Li, Mengwen; Ning, Yashan; Yu, Zhilin; Wang, Yinsong; Wang, Hao
• Is Part Of: Nano today. Volume 33(2020)
• Publication Date: 2020-08
• Subjects: Self-assembly -- Peptides -- Drug delivery -- Cancer therapy -- Morphological transition; Nanotechnology -- Periodicals; Nanosciences -- Périodiques; 620.505
• DOI: 10.1016/j.nantod.2020.100878
• Languages: English
• ISSNs: 1748-0132

Abstract

Graphical abstract: Highlights: Co-assembly of peptide AmpF with its two derivatives into nanomedicines with morphologies ultra-sensitive to medium pH. Uptaking nanomedicines via an endo-/lysosome-mediated pathway renders their morphology adaptable to tissue/organelle pH. The adaptable nanomedicines prolonged blood circulation and facilitated tumor penetration and accumulation. The improved delivering efficiency led to enhanced combinatorial chemo-photodynamic therapy against breast tumors. Abstract: 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 photosensitizer 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 chemo-photodynamic 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.