Facial Layer-by-Layer Engineering of Upconversion Nanoparticles for Gene Delivery: Near-Infrared-Initiated Fluorescence Resonance Energy Transfer Tracking and Overcoming Drug Resistance in Ovarian Cancer.
Development of multidrug resistance (MDR) contributes to the majority of treatment failures in clinical chemotherapy. We report facial layer-by-layer engineered upconversion nanoparticles (UCNPs) for near-infrared (NIR)-initiated tracking and delivery of small interfering RNA (siRNA) to enhance chemotherapy efficacy by silencing the MDR1 gene and resensitizing resistant ovarian cancer cells to drug. Layer-by-layer engineered UCNPs were loaded with MDR1 gene-silencing siRNA (MDR1-siRNA) by electrostatic interaction. The delivery vehicle enhances MDR1-siRNA cellular uptake, protects MDR1-siRNA from nuclease degradation, and promotes endosomal escape for silencing the MDR gene. The intrinsic photon upconversion of UCNPs provides an unprecedented opportunity for monitoring intracellular attachment and release of MDR1-siRNA by NIR-initiated fluorescence resonance energy transfer occurs between donor UCNPs and acceptor fluorescence dye-labeled MDR1-siRNA. Enhanced chemotherapeutic efficacy in vitro was demonstrated by cell viability assay. The developed delivery vehicle holds great potential in delivery and imaging-guided tracking of therapeutic gene targets for effective treatment of drug-resistant cancers.
Min
http://orcid.org/0000-0002-3259-1955
M
Lin
Yan
Y
Gao
Ragon Institute of MGH, Massachusetts Institute of Technology (MIT) and Harvard University , Boston, Massachusetts 02139, United States.
Thomas J
TJ
Diefenbach
Jacson K
JK
Shen
Francis J
FJ
Hornicek
School of Chemical Engineering, Chonnam National University , Gwangju 61186, Republic of Korea.
Yong Il
YI
Park
Feng
http://orcid.org/0000-0003-4351-0222
F
Xu
Tian Jian
TJ
Lu
Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University , Boston, Massachusetts 02115, United States.
Mansoor
M
Amiji
Zhenfeng
Z
Duan
D019008:Drug Resistance, Neoplasm; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D018014:Gene Transfer Techniques; D006801:Humans; D053758:Nanoparticles; D010051:Ovarian Neoplasms; D034741:RNA, Small Interfering
D034741:RNA, Small Interfering
FRET; drug sensitivity; gene delivery; gene knockdown; upconversion nanoparticles