期刊
THERANOSTICS
卷 8, 期 11, 页码 2939-2953出版社
IVYSPRING INT PUBL
DOI: 10.7150/thno.24015
关键词
ROS responsive; chemo-photodynamic therapy; on-demand drug release; drug-resistant cancer; synergistic therapy
资金
- National Natural Science Foundation of China [51603150, 51473043, 51773067]
- National Key R&D Program of China [2017YFA0205601]
- Tianjin Municipal Science and Technology Commission [17JCQNJC02200]
The simple integration of chemotherapeutic drugs and photosensitizers (PSs) into the same nanocarriers only achieves a combination of chemo-photodynamic therapy but may not confer synergistic effects. The boosted intracellular release of chemotherapeutic drugs during the photodynamic therapy (PDT) process is necessary to achieve a cascade of amplified synergistic therapeutic effects of chemo-photodynamic therapy. Methods: In this study, we explored an innovative hyperbranched polyphosphate (RHPPE) containing a singlet oxygen (SO)-labile crosslinker to boost drug release during the PDT process. The photosensitizer chlorin e6 (Ce6) and doxorubicin (DOX) were simultaneously loaded into RHPPE nanoparticles (denoted as (HNPCe6/DOX)-H-SO). The therapeutic efficacy of (HNPCe6/DOX)-H-SO against drug-resistant cancer was evaluated in vitro and in vivo. Results: Under 660-nm light irradiation, (HNPCe6/DOX)-H-SO can produce SO, which not only induces PDT against cancer but also cleaves the thioketal linkers to destroy the nanoparticles. Subsequently, boosted DOX release can be achieved, activating a chemotherapy cascade to synergistically destroy the remaining tumor cells after the initial round of PDT. Furthermore, (HNPCe6/DOX)-H-SO also efficiently detected the tumor area by photoacoustic/magnetic resonance bimodal imaging. Under the guidance of bimodal imaging, the laser beam was precisely focused on the tumor areas, and subsequently, (HNPCe6/DOX)-H-SO realized a cascade of amplified synergistic chemo-photodynamic therapeutic effects. High antitumor efficacy was achieved even in a drug-resistant tumor model. Conclusion: The designed (HNPCe6/DOX)-H-SO with great biocompatibility is promising for use as a co-delivery carrier for combined chemo-photodynamic therapy, providing an alternative avenue to achieve a cascade of amplified synergistic effects of chemo-photodynamic therapy for cancer treatment.
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