Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 11, Issue 12, Pages 11112-11118Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b21724
Keywords
DNA origami; RNase A; self-assembly; protein delivery; cancer therapy
Funding
- National Basic Research Programs of China [2016YFA0201601, 2018YFA0208900]
- National Natural Science Foundations of China [21573051, 31700871, 21708004, 51761145044]
- Science Fund for Creative Research Groups of the National Natural Science Foundation of China [21721002]
- Beijing Municipal Science & Technology Commission [Z161100000116036]
- Key Research Program of Frontier Sciences, CAS [QYZDB-SSW-SLH029]
- CAS Interdisciplinary Innovation Team
- K. C. Wong Education Foundation
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Delivery of proteins to carry out desired biological functions is a direct approach for disease treatment. However, protein therapy is still facing challenges due to low delivery efficiency, poor targeting during trafficking, insufficient therapeutic efficacy, and possible toxicity induced by carriers. Here, we present a novel delivery platform based on DNA origami nanostructure that enables tumor cell transportation of active proteins for cancer therapy. In our design, cytotoxic protein ribonuclease (RNase) A molecules are organized on the rectangular DNA origami nanosheets, which work as nanovehicles to deliver RNase A molecules into the cytoplasm and execute their cell-killing function inside the tumor cells. Cancer cell-targeting aptamers are also integrated onto the DNA origami-based nanoplatform to enhance its targeting effect. This DNA origami protein coassembling strategy can be further developed to transport other functional proteins and therapeutic components simultaneously for synergistic effects and be adapted for integrated diagnostics and therapeutics.
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