DataVXACS Applied Materials & InterfacesPaper
journal article·2021-02-24

CRISPR-dCas9-Guided and Telomerase-Responsive Nanosystem for Precise Anti-Cancer Drug Delivery

Yingxin Ma, Guobin Mao, Guoqiang Wu, Zongqiang Cui, Xian-En Zhang, Weiren Huang

ACS Applied Materials & Interfaces· Volume 13· Issue 7
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Source abstract

Abstract

Nanodrug delivery systems are very promising for highly efficient anticancer drug delivery. However, the present nanosystems are commonly located in the cytoplasm and mediate uncontrolled release of drugs into cytosol, while a large number of anticancer drugs function more efficiently inside the nucleus. Here, we constructed a CRISPR-dCas9-guided and telomerase-responsive nanosystem for nuclear targeting and smart release of anticancer drugs. CRISPR-dCas9 technology has been employed to achieve conjugation of mesoporous silica nanoparticles (MSNs) with a high payload of the active anticancer drug, doxorubicin (DOX). A specifically designed wrapping DNA was used as a telomerase-responsive biogate to encapsulate DOX within MSNs. The wrapping DNA is extended in the presence of telomerase, which is highly activated in tumor cells, but not in normal cells. The extended DNA sequence forms a rigid hairpin-like structure and diffuses away from the MSN surface. CRISPR-dCas9 specifically targets telomere-repetitive sequences at the tips of chromosomes, facilitating the precise delivery of the nanosystem to the nucleus, and effective drug release triggered by telomerase that was enriched around telomeric repeats. This study provides a strategy and nanosystem for nuclear-targeted delivery and tumor-specific release of anticancer drugs that will maximize the efficiency of cancer cell destruction.
Source: openalex_inverted_index · Quality: baseline

Research context

Nanomaterials

OpenAlex topics: Advanced biosensing and bioanalysis techniques · RNA Interference and Gene Delivery · CRISPR and Genetic Engineering

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen University School of Medicine, Shenzhen 518055, China

CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China

State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China

National Key Laboratory of Biomacromolecules, CAS Center for Biological Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China

Funding

China Postdoctoral Science Foundation · Health and Family Planning Commission of Shenzhen Municipality · National Natural Science Foundation of China · Natural Science Foundation of Guangdong Province · Department of S and T for Social Development · Chinese Academy of Sciences · Shenzhen Municipal Government of China · Shenzhen Institute of Synthetic Biology Scientific Research Program · Sanming Project of Shenzhen Health and Family Planning Commission · High Level University’s Medical Discipline Construction

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