10.1002/anie.202008732
Angewandte Chemie International Edition
RESEARCH ARTICLE
well-defined spherical morphology, which presented effective
tumor accumulation. Under hypoxic environment, the
encapsulated PTX2-Azo could be cleaved to free PTX. The co-
encapsulated Ce6 could generate 1O2 to induce cell apoptosis
and simultaneous oxygen consumption aggravated hypoxia,
which further promoted the release of PTX. The Ce6/PTX2-Azo
NPs possess enhanced cytotoxicity against HeLa, MCF-7 and
C643 cells, and superior in vivo antitumor efficacy with no
obvious systemic toxicity. In brief, the prepared Ce6/PTX2-Azo
NP represents hypoxia-activatable prodrug system, which takes
full advantages of the characteristics of tumor hypoxia and
compensates the deficiency of PDT. Meanwhile, the synergetic
PDT and chemotherapy achieves maximized therapeutic
efficacy and minimized side effects, which is promising in clinical
medicines.
Acknowledgements
Figure 5. Biodistribution of NPs and in vivo anticancer efficacy evaluation. a)
Time-dependent NIR fluorescence images of tumor-bearing nude mice after i.v.
administration of free Ce6, Ce6 NP or Ce6/PTX2-Azo NP (Ce6: 10 mg/kg); b)
Ex vivo NIR fluorescence images of major organs and tumor excised at 30 h
post injection; c) Photographs of tumors collected from mice after 30 days; d)
Tumor growth curves for mice upon different treatments (Ce6: 10 mg/kg,
PTX2-Azo: 50 mg/kg); e) Average tumor weights for each group after 30 days
treatment; f ) H&E stained images of tumor slices collected at the end of the
experiment. Scale bar, 100 μm. Data are expressed as mean SD (n=5).
***P< 0.001 and **P< 0.01.
This work was supported by the National Natural Science
Foundation of China (Project No. 51773197, 51973213 and
51973214).
Keywords: paclitaxel • combination therapy • hypoxia • prodrugs
• photodynamic therapy
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Conclusion
In summary, we have designed a hypoxia-activated dimeric
prodrug PTX2-Azo and explored its combination with PDT for
synergistic photodynamic-chemotherapy. The as-prepared
Ce6/PTX2-Azo NP with size of approximately 100 nm exhibited
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5
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