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Light-triggered dual-modality drug release of self-assembled prodrug-nanoparticles for synergistic photodynamic and hypoxia-activated therapy

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Abstract

Photodynamic therapy (PDT) leads to tumor hypoxia which could be utilized for the activation of hypoxia-activated prodrugs (HAPs). However, conventional photosensitizer-loaded nanoformulations suffer from an aggregation-caused quenching (ACQ) effect, which limits the efficiency of PDT and synergistic therapy. Herein, prodrug-nanoparticles (NPs) are prepared by the self-assembly of heterodimeric prodrugs composed of pyropheophorbide a (PPa), hypoxia-activated prodrug PR104A, and a thioether or thioketal linkage. In addition, a novel dual-modality drug release pattern is proposed on the basis of the structural states of prodrug-NPs. Under light irradiation, PR104A is released via photoinduced electron transfer (PET) due to the aggregation state of prodrugs. With the disassembly of prodrug-NPs, the ACQ effect is relieved, and PPa produces singlet oxygen which further promotes the reactive oxygen species (ROS)-sensitive release of PR104A. Such prodrug-NPs turn the disadvantage of the ACQ effect to facilitate drug release, demonstrating high-efficiency synergy in combination with PDT and hypoxia-activated therapy.

Graphical abstract: Light-triggered dual-modality drug release of self-assembled prodrug-nanoparticles for synergistic photodynamic and hypoxia-activated therapy

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Supplementary files

Article information


Submitted
17 Jan 2020
Accepted
16 Mar 2020
First published
17 Mar 2020

Nanoscale Horiz., 2020, Advance Article
Article type
Communication

Light-triggered dual-modality drug release of self-assembled prodrug-nanoparticles for synergistic photodynamic and hypoxia-activated therapy

D. Zhao, W. Tao, S. Li, L. Li, Y. Sun, G. Li, G. Wang, Y. Wang, B. Lin, C. Luo, Y. Wang, M. Cheng, Z. He and J. Sun, Nanoscale Horiz., 2020, Advance Article , DOI: 10.1039/D0NH00034E

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