A Nanobody-Conjugated DNA Nanoplatform for Targeted Platinum-Drug Delivery

Tiantian Wu; Jianbing Liu; Manman Liu; Shaoli Liu; Shuai Zhao; Run Tian; Dengshuai Wei; Yangzhong Liu; Yao Zhao; Haihua Xiao; Baoquan Ding

doi:10.1002/anie.201909345

A Nanobody-Conjugated DNA Nanoplatform for Targeted Platinum-Drug Delivery

Angew Chem Int Ed Engl. 2019 Oct 1;58(40):14224-14228. doi: 10.1002/anie.201909345. Epub 2019 Aug 27.

Authors

Tiantian Wu^{1

2}, Jianbing Liu¹, Manman Liu³, Shaoli Liu^{1

2}, Shuai Zhao^{1

2}, Run Tian^{1

2}, Dengshuai Wei⁴, Yangzhong Liu³, Yao Zhao⁵, Haihua Xiao⁴, Baoquan Ding^{1

2}

Affiliations

¹ CAS Key Laboratory of Nanosystem and Hierarchical Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, 11 BeiYiTiao, ZhongGuanCun, Beijing, 100190, China.
² University of Chinese Academy of Sciences, Beijing, 100049, China.
³ CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China.
⁴ Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
⁵ Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.

PMID: 31389144
DOI: 10.1002/anie.201909345

Abstract

The targeted delivery of chemotherapeutic drugs is a major challenge in the clinical treatment of cancer. Herein, we constructed a multifunctional DNA nanoplatform as a versatile carrier of the highly potent platinum-based DNA intercalator, 56MESS. In our rational design, 56MESS was efficiently loaded into the double-bundle DNA tetrahedron through intercalation with the DNA duplex. With the integration of a nanobody that both targets and blocks epidermal growth factor receptor (EGFR), the DNA nanocarriers exhibit excellent selectivity for cells with elevated EGFR expression (a common biomarker related to tumor formation) and combined tumor therapy without obvious systemic toxicity. This DNA-based platinum-drug delivery system provides a promising strategy for the treatment of tumors.

Keywords: DNA nanotechnology; cancer therapy; drug delivery; nanobody; platinum.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Carcinoma, Squamous Cell / drug therapy*
Carcinoma, Squamous Cell / metabolism
Carcinoma, Squamous Cell / pathology
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Survival / drug effects
DNA / chemistry*
Drug Carriers / chemistry
Drug Delivery Systems*
Drug Screening Assays, Antitumor
ErbB Receptors / antagonists & inhibitors
ErbB Receptors / genetics
ErbB Receptors / metabolism
Humans
Nanostructures / chemistry*
Organoplatinum Compounds / chemical synthesis
Organoplatinum Compounds / chemistry
Organoplatinum Compounds / pharmacology*

Substances

Antineoplastic Agents
Drug Carriers
Organoplatinum Compounds
DNA
EGFR protein, human
ErbB Receptors