Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 14, Issue 5, Pages 6387-6403Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c22620
Keywords
anthraquinone; drug delivery; DNA origami; photoacoustic imaging; tumor hypoxia
Funding
- National Key R&D Program of China [2018YFC0910600]
- National Natural Science Foundation of China [11727813, 91859109, 32001074]
- Open Funding Project of National Key Laboratory of Human Factors Engineering [SYFD061908K]
- Natural Science Basic Research Plan in Shaanxi Province of China [2020JM-209]
- Fundamental Research Funds for the Central Universities [JB211206, JB211205]
- Science and Technology Plan Project of Xi'an [21YXYJ0065]
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In this study, we developed a DNA origami-based theranostic nanoplatform to explain the variation of tumor hypoxia during chemotherapy. Through in vitro and in vivo experiments, we demonstrated that the nanoplatform can release drugs and alleviate tumor hypoxia. Photoacoustic and fluorescence imaging were used to evaluate these effects.
Hypoxia is a well-known feature of malignant solid tumors. To explain the misinterpretation of tumor hypoxia variation during chemotherapy, we developed a DNA origami-based theranostic nanoplatform with an intercalated anticancer anthraquinone as both the chemotherapeutic drug and the photoacoustic contrast agent. The size distribution of the DNA origami nanostructure is 44.5 +/- 2.3 nm, whereas the encapsulation efficiency of the drug is 90.7 +/- 1.0%, and the drug loading content is 92.2 +/- 0.1%. The controlled cumulative release rates were measured in vitro, showing an acidic environment induced rapid drug release. The values of free energy of binding between the drugs and the DNA double helix were calculated through molecular simulations. The cell viability assay was used to characterize cytotoxicity, and fluorescence confocal cell imaging illustrates the biodistribution of the probe in vitro. Photoacoustic and fluorescence imaging were used to indicate drug delivery, release, and biodistribution to predict the drug's chemotherapeutic effect in vivo, whereas the photoacoustic signals were compared with those of deoxygenated/oxygenated hemoglobin to represent the tissue hypoxia/normoxia maps during the chemotherapeutic process and indicate alleviated tumor hypoxia. Staining of tissue sections taken from organs and tumors was used to verify the results of photoacoustic imaging. Our results suggest that photoacoustic imaging can visualize this DNA origami-based theranostic nanoplatform and reveal the mechanisms of chemotherapy on tumor hypoxia.
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