Aptamer Functionalized Upconversion Nanotheranostic Agent With Nuclear Targeting as the Highly Localized Drug-Delivery System of Doxorubicin

被引:12
作者
Song, Xinyue [1 ,2 ]
Yan, Tao [1 ]
Tian, Feng [1 ]
Li, Fengyan [1 ]
Ren, Linlin [1 ]
Li, Qiong [1 ,2 ]
Zhang, Shusheng [1 ]
机构
[1] Linyi Univ, Shandong Prov Key Lab Detect Technol Tumor Marker, Coll Chem & Chem Engn, Linyi, Shandong, Peoples R China
[2] Qingdao Univ, Mobile Postdoctoral Ctr, Mat Sci & Engn, Qingdao, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
aptamers; doxorubicin; drug delivery; nuclear targeting; upconversion nanotheranostic agent;
D O I
10.3389/fbioe.2021.639487
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
As a widely used anticancer drug, doxorubicin (DOX) could induce cell death mainly via interfering with DNA activity; thus, DOX could perform therapeutic effects mainly in the cell nucleus. However, most of the reported drug delivery systems lacked the well localization in the nucleus and released DOX molecules into the cytoplasm. Due to formidable barriers formed in the nuclear envelope, only around 1% of DOX could reach the nucleus and keep active. Therefore, DOX molecules were inevitably overloaded to achieve the desired therapeutic efficacy, which would induce serious side effects. Herein, we developed a highly localized drug nanocarrier for in situ release of DOX molecules to their action site where they could directly interfere with the DNA activity. In this work, we used cationic polymer-modified upconversion nanoparticles (UCNPs) as the luminescence core and gene carrier, while aptamers served as the DNA nanotrain to load DOX. Finally, the prepared nanotheranostic agent displayed good targetability, high cell apoptosis ratio (93.04%) with quite lower concentration than the LC50 of DOX, and obvious inhibition on tumor growth.
引用
收藏
页数:12
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共 38 条
[1]   Extracellularly activatable nanocarriers for drug delivery to tumors [J].
Abouelmagd, Sara A. ;
Hyun, Hyesun ;
Yeo, Yoon .
EXPERT OPINION ON DRUG DELIVERY, 2014, 11 (10) :1601-1618
[2]   Doxorubicin: The Good, the Bad and the Ugly Effect [J].
Carvalho, Cristina ;
Santos, Renato X. ;
Cardoso, Susana ;
Correia, Sonia ;
Oliveira, Paulo J. ;
Santos, Maria S. ;
Moreira, Paula I. .
CURRENT MEDICINAL CHEMISTRY, 2009, 16 (25) :3267-3285
[3]   PREFERENTIAL BINDING OF DAUNOMYCIN TO 5'ATCG AND 5'ATGC SEQUENCES REVEALED BY FOOTPRINTING TITRATION EXPERIMENTS [J].
CHAIRES, JB ;
HERRERA, JE ;
WARING, MJ .
BIOCHEMISTRY, 1990, 29 (26) :6145-6153
[4]   Tumor therapy: targeted drug delivery systems [J].
Dai, Liangliang ;
Liu, Junjie ;
Luo, Zhong ;
Li, Menghuan ;
Cai, Kaiyong .
JOURNAL OF MATERIALS CHEMISTRY B, 2016, 4 (42) :6758-6772
[5]   Fabrication of fluorescent composite hydrogel using in situ synthesis of upconversion nanoparticles [J].
Dong, Yuqing ;
Lin, Min ;
Jin, Guorui ;
Park, Yong Il ;
Qiu, Mushu ;
Zhao, Ying ;
Yang, Hui ;
Li, Ang ;
Lu, Tian Jian .
NANOTECHNOLOGY, 2017, 28 (17)
[6]   Upconverting Nanoparticles [J].
Haase, Markus ;
Schaefer, Helmut .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2011, 50 (26) :5808-5829
[7]   A Drug-Loaded Aptamer-Gold Nanoparticle Bioconjugate for Combined CT Imaging and Therapy of Prostate Cancer [J].
Kim, Dongkyu ;
Jeong, Yong Yeon ;
Jon, Sangyong .
ACS NANO, 2010, 4 (07) :3689-3696
[8]   Aptamer-Mediated Delivery of Splice-Switching Oligonucleotides to the Nuclei of Cancer Cells [J].
Kotula, Jonathan W. ;
Pratico, Elizabeth D. ;
Ming, Xin ;
Nakagawa, Osamu ;
Juliano, Rudolph L. ;
Sullenger, Bruce A. .
NUCLEIC ACID THERAPEUTICS, 2012, 22 (03) :187-195
[9]   Inhibition of DNA replication by an anti-PCNA aptamer/PCNA complex [J].
Kowalska, Ewa ;
Bartnicki, Filip ;
Fujisawa, Ryo ;
Bonarek, Piotr ;
Hermanowicz, Pawel ;
Tsurimoto, Toshiki ;
Muszynska, Klaudia ;
Strzalka, Wojciech .
NUCLEIC ACIDS RESEARCH, 2018, 46 (01) :25-41
[10]   BIOLOGICAL MARKERS Potential biomarker for aspirin use in colorectal cancer therapy [J].
Langley, Ruth E. ;
Rothwell, Peter M. .
NATURE REVIEWS CLINICAL ONCOLOGY, 2013, 10 (01) :8-10