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Light-Activatable Dual-Source ROS-Responsive Prodrug Nanoplatform for Synergistic Chemo-Photodynamic Therapy


In view of prodrug nanomedicines for cancer therapy, one of the great challenges is the slow and variable release of the parent drug in tumors. Recently, many smart redox-sensitive nanocarriers are developed to address this dilemma. However, due to significant tumor heterogeneity, some redox-sensitive nanomedicines still show poor selectivity in drug release. Herein, we report a ROS-triggered prodrug nanoplatform fabricated by oxidation-responsive cabazitaxel (CTX) prodrugs for synergistic chemo-photodynamic therapy, thioether-/selenoether-linked conjugates of CTX and oleic acid (OA) are designed and synthesized, and these prodrugs can readily self-assembled into nanoparticles, with pyropheophorbide a (PPa) co-encapsulated into the prodrug-nanosystem for combination therapy. The dual-source ROS-responsive prodrug nanosystems selectively and rapidly release CTX not only in response to the endogenous ROS overproduced in tumor cells, but also to the exogenous PPa-generated ROS under laser irradiation. Moreover, selenium-containing linkage demonstrates significant advantages over the sulfur-containing linkage in terms of ROS-triggered drug release and cytotoxicity. The prepared prodrug-nanosystems significantly prolong the systemic circulation and tumor distribution of both CTX and PPa, thereby demonstrating synergistic chemo-photodynamic therapy in vivo. All these drug delivery advantages render the nanosystem extremely promising for cancer treatment.

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Publication details

The article was received on 31 Jul 2018, accepted on 07 Sep 2018 and first published on 12 Sep 2018

Article type: Paper
DOI: 10.1039/C8BM00899J
Citation: Biomater. Sci., 2018, Accepted Manuscript
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    Light-Activatable Dual-Source ROS-Responsive Prodrug Nanoplatform for Synergistic Chemo-Photodynamic Therapy

    B. Yang, K. Wang, D. Zhang, B. Sun, B. Ji, L. Wei, Z. Li, M. Wang, X. Zhang, H. Zhang, Q. Kan, C. Luo, Y. Wang, Z. He and J. Sun, Biomater. Sci., 2018, Accepted Manuscript , DOI: 10.1039/C8BM00899J

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