| Title |
Enhancing siRNA-based cancer therapy using a new pH-responsive activatable cell-penetrating peptide-modified liposomal system
|
|---|---|
| Published in |
International Journal of Nanomedicine, March 2017
|
| DOI | 10.2147/ijn.s129574 |
| Pubmed ID | |
| Authors |
Bai Xiang, Xue-Li Jia, Jin-Long Qi, Li-Ping Yang, Wei-Hong Sun, Xiao Yan, Shao-Kun Yang, De-Ying Cao, Qing Du, Xian-Rong Qi |
| Abstract |
As a potent therapeutic agent, small interfering RNA (siRNA) has been exploited to silence critical genes involved in tumor initiation and progression. However, development of a desirable delivery system is required to overcome the unfavorable properties of siRNA such as its high degradability, molecular size, and negative charge to help increase its accumulation in tumor tissues and promote efficient cellular uptake and endosomal/lysosomal escape of the nucleic acids. In this study, we developed a new activatable cell-penetrating peptide (ACPP) that is responsive to an acidic tumor microenvironment, which was then used to modify the surfaces of siRNA-loaded liposomes. The ACPP is composed of a cell-penetrating peptide (CPP), an acid-labile linker (hydrazone), and a polyanionic domain, including glutamic acid and histidine. In the systemic circulation (pH 7.4), the surface polycationic moieties of the CPP (polyarginine) are "shielded" by the intramolecular electrostatic interaction of the inhibitory domain. When exposed to a lower pH, a common property of solid tumors, the ACPP undergoes acid-catalyzed breakage at the hydrazone site, and the consequent protonation of histidine residues promotes detachment of the inhibitory peptide. Subsequently, the unshielded CPP would facilitate the cellular membrane penetration and efficient endosomal/lysosomal evasion of liposomal siRNA. A series of investigations demonstrated that once exposed to an acidic pH, the ACPP-modified liposomes showed elevated cellular uptake, downregulated expression of polo-like kinase 1, and augmented cell apoptosis. In addition, favorable siRNA avoidance of the endosome/lysosome was observed in both MCF-7 and A549 cells, followed by effective cytoplasmic release. In view of its acid sensitivity and therapeutic potency, this newly developed pH-responsive and ACPP-mediated liposome system represents a potential platform for siRNA-based cancer treatment. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 72 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 72 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 18 | 25% |
| Student > Bachelor | 13 | 18% |
| Student > Master | 9 | 13% |
| Researcher | 5 | 7% |
| Other | 1 | 1% |
| Other | 4 | 6% |
| Unknown | 22 | 31% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 12 | 17% |
| Biochemistry, Genetics and Molecular Biology | 10 | 14% |
| Medicine and Dentistry | 6 | 8% |
| Chemistry | 5 | 7% |
| Agricultural and Biological Sciences | 3 | 4% |
| Other | 12 | 17% |
| Unknown | 24 | 33% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 March 2017.
All research outputs
#20,660,571
of 25,382,440 outputs
Outputs from International Journal of Nanomedicine
#3,127
of 4,122 outputs
Outputs of similar age
#251,546
of 324,443 outputs
Outputs of similar age from International Journal of Nanomedicine
#70
of 95 outputs
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