Abstract
Simultaneous silencing of multiple apoptosis-related genes is an attractive approach to treat cancer. In this article, we present a multiple gene-targeting siRNA/drug delivery system for prostate cancer treatment with a high efficiency. Bcl-2, survivin, and androgen receptor genes involved in the cell apoptosis pathways were chosen as silencing targets with three different siRNAs. The colloidal nanocomplex delivery system (<10 nm in size) was formulated electrostatically between anionic siRNAs and a cationic drug (BZT), followed by encapsulation with the Pluronic F-68 polymer. The formulated nanocomplex system exhibited sufficient stability against nuclease-induced degradation, leading to successful intracellular delivery for the desired therapeutic performance. Silencing of targeted genes and apoptosis induction were evaluated in vitro on human prostate LNCaP-LN3 cancer cells by using various biological analysis tools (e.g., real-time PCR, MTT cell viability test, and flow cytometry). It was demonstrated that when the total loaded siRNA amounts were kept the same in the nanocomplexes, the simultaneous silencing of triple genes with co-loaded siRNAs (i.e., Bcl-2, survivin, and AR-targeting siRNAs) enhanced BZT-induced apoptosis of cancer cells more efficiently than the silencing of each single gene alone, offering a novel way of improving the efficacy of gene therapeutics including anticancer drug.
| Original language | English |
|---|---|
| Pages (from-to) | 3777-3785 |
| Number of pages | 9 |
| Journal | Molecular Pharmaceutics |
| Volume | 15 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - 2018 Sept 4 |
| Externally published | Yes |
Bibliographical note
Funding Information:This work was supported by grants from the Korea Health Industry Development Institute (HI15C1540), the Development of Platform Technology for Innovative Medical Measurements Program from Korea Research Institute of Standards and Science (KRISS-2017-GP2017-0020) and the National Research Foundation of Korea (no. H-GUARD-2014- M3A6B2060522). The authors thank Dr. Yeong-Su Jang and Dr. Mihue Jang for helpful discussion during the gene silencing experiment and specially thank Dr. Seo-Young Kwak for her kind help during Western blotting.
Funding Information:
This work was supported by grants from the Korea Health Industry Development Institute (HI15C1540), the Development of Platform Technology for Innovative Medical Measurements Program from Korea Research Institute of Standards and Science (KRISS-2017-GP2017-0020), and the National Research Foundation of Korea (no. H-GUARD_2014-M3A6B2060522). The authors thank Dr. Yeong-Su Jang and Dr. Mihue Jang for helpful discussion during the gene silencing experiment and specially thank Dr. Seo-Young Kwak for her kind help during Western blotting.
Publisher Copyright:
Copyright © 2018 American Chemical Society.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
Keywords
- Bcl-2
- androgen receptor
- drug delivery
- gene silencing
- prostate cancer
- survivin
ASJC Scopus subject areas
- Molecular Medicine
- Pharmaceutical Science
- Drug Discovery
