Abstract:Non-viral carrier systems, especially nanoparticles, have been investigated extensively for siRNA delivery, and may be utilized in clinical applications in the future. So far, a few preliminary clinical trials of nanoparticles have produced promising results. However, further research is still required to pave the way to successful clinical applications. The most important issues that need to be focused on include encapsulation efficiency, formulation stability of siRNA, degradation in circulation, endosomal e… Show more
“…Ideally, this carrier should also provide protection of the nucleic acids against enzymatic degradation during the different steps of the delivery process. In the field of nonviral gene delivery, liposomal and polymeric delivery systems (known as lipoplexes and polyplexes, respectively) have a long history [93]. Compared to viral delivery systems, both lipo-and polyplexes are generally easy to prepare, not or weakly immunogenic and allow the incorporation of larger DNA chains as there is no intrinsic size limitation as with viral particles [13].…”
Section: Mitotic Partitioning Of Inorganic Quantum Dots Gold and Iromentioning
“…Ideally, this carrier should also provide protection of the nucleic acids against enzymatic degradation during the different steps of the delivery process. In the field of nonviral gene delivery, liposomal and polymeric delivery systems (known as lipoplexes and polyplexes, respectively) have a long history [93]. Compared to viral delivery systems, both lipo-and polyplexes are generally easy to prepare, not or weakly immunogenic and allow the incorporation of larger DNA chains as there is no intrinsic size limitation as with viral particles [13].…”
Section: Mitotic Partitioning Of Inorganic Quantum Dots Gold and Iromentioning
“…17,18 One advantage of PLGA NPs is that they can be directly coated with cationic polymers, such as polyethylenimine (PEI), enabling them to carry siRNA on their surfaces through electrostatic interactions. 19,20 Therefore, PLGA-PEI NPs could be used as a carrier that integrates anticancer drugs (inner part) and agents to reduce chemoresistance, eg, siRNA (outer layer).…”
Background: Effective cancer chemotherapy remains an important issue in cancer treatment, and signal transducer and activator of transcription-3 (Stat3) activation leads to cellular resistance of anticancer agents. Polymers are ideal vectors to carry both chemotherapeutics and small interfering ribonucleic acid (siRNA) to enhance antitumor efficacy. In this paper, poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with paclitaxel and Stat3 siRNA were successfully synthesized, and their applications in cancer cells were investigated. Methods: Firstly, paclitaxel was enclosed by PLGA nanoparticles through solvent evaporation. They were then coated with cationic polyethylenimine polymer (PLGA-PEI-TAX), enabling it to carry Stat3 siRNA on its surface through electrostatic interactions (PLGA-PEI-TAX-S3SI). The size, zeta potential, deliver efficacy, and release profile of the PLGA nanocomplexes were characterized in vitro. The cellular uptake, intracellular nanoparticle trajectory, and subsequent cellular events were evaluated after treatment with various PLGA nanocomplexes in human lung cancer A549 cells and A549-derived paclitaxel-resistant A549/T12 cell lines with α-tubulin mutation. Results: A549 and A549/T12 cells contain constitutively activated Stat3, and silencing Stat3 by siRNA made both cancer cells more sensitive to paclitaxel. Therefore, PLGA-PEI-TAX-S3SI was synthesized to test its therapeutic role in A549 and A549/T12 cells. Transmission electron microscopy showed the size of PLGA-PEI-TAX-S3SI to be around 250 nm. PLGA-PEI nanoparticles were nontoxic. PLGA-PEI-TAX was taken up by A549 and A549/T12 cells more than free paclitaxel, and they induced more condensed microtubule bundles and had higher cytotoxicity in these cancer cells. Moreover, the yellowish fluorescence observed in the cytoplasm of the cancer cells indicates that the PLGA-PEI nanoparticles were still simultaneously delivering Oregon Green paclitaxel and cyanine-5-labeled Stat3 siRNA 3 hours after treatment. Furthermore, after the cancer cells were incubated with the synthesized PLGA nanocomplexes, PLGA-PEI-TAX-S3SI suppressed Stat3 expression and induced more cellular apoptosis in A549 and A549/T12 cells compared with PLGA-PEI-TAX.
Conclusion:The PLGA-PEI-TAX-S3SI complex provides a new therapeutic strategy to control cancer cell growth.
“…These antibody-siRNA molecules were able to specifically target and enter envelope-expressing cells in mice (Song et al, 2005). And many techniques for introducing siRNA into nanoparticles have been tested for better pharmacokinetics, but these have been mainly preclinical studies not involving HIV-1 (reviewed in Yuan et al, 2011).…”
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.