| Title |
Targeted delivery of siRNA using transferrin-coupled lipoplexes specifically sensitizes CD71 high expressing malignant cells to antibody-mediated complement attack
|
|---|---|
| Published in |
Targeted Oncology, November 2014
|
| DOI | 10.1007/s11523-014-0345-6 |
| Pubmed ID | |
| Authors |
Marc Cinci, Srinivas Mamidi, Wenhan Li, Volker Fehring, Michael Kirschfink |
| Abstract |
The overexpression of membrane-bound complement regulatory proteins (mCRP; CD46, CD55, CD59) preventing opsonization and complement-dependent cytotoxicity (CDC) is considered a major barrier for successful antibody-based cancer immunotherapy. To avoid a potential deleterious effect of mCRP neutralization on normal tissue cells, complement regulation has to be selectively targeted to the malignant cells. In this study, anti-mCRP small interfering RNAs (siRNAs) were encapsulated in transferrin-coupled lipoplexes for the specific delivery to transferrin receptor CD71(high) expressing BT474, DU145, and SW480 as well as corresponding CD71-knockdown (CD71(low)) tumor cells. Targeted delivery with transferrin-siRNA-lipoplexes became possible by charge neutralization and resulted in efficient silencing of all three mCRPs up to 90 %, which is dependent on their CD71 expression. The mCRP knockdown led to a significant increase of CDC on CD71(high) tumor cells by 68 % in BT474, 58 % in DU145, and 40 % in SW480 cells but only slightly increased on CD71(low) cells. Downregulation of CD46 and CD55 significantly increased C3 opsonization only on CD71(high) tumor cells. Our results demonstrate for the first time that by specific delivery of anti-mCRP siRNA through transferrin receptor, complement regulation can be selectively neutralized, allowing specific antibody-mediated killing of tumor cells without affecting healthy bystander cells, which appears to be a suited strategy to improve antibody-based cancer immunotherapy. |
X Demographics
The data shown below were collected from the profiles of 2 X users 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 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Scientists | 1 | 50% |
| Practitioners (doctors, other healthcare professionals) | 1 | 50% |
Mendeley readers
The data shown below were compiled from readership statistics for 24 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 24 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 4 | 17% |
| Student > Ph. D. Student | 4 | 17% |
| Student > Bachelor | 3 | 13% |
| Student > Doctoral Student | 2 | 8% |
| Other | 2 | 8% |
| Other | 3 | 13% |
| Unknown | 6 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 6 | 25% |
| Agricultural and Biological Sciences | 4 | 17% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 4% |
| Business, Management and Accounting | 1 | 4% |
| Chemical Engineering | 1 | 4% |
| Other | 4 | 17% |
| Unknown | 7 | 29% |
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 01 January 2015.
All research outputs
#15,330,390
of 23,577,654 outputs
Outputs from Targeted Oncology
#257
of 567 outputs
Outputs of similar age
#144,029
of 258,556 outputs
Outputs of similar age from Targeted Oncology
#3
of 7 outputs
Altmetric has tracked 23,577,654 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 567 research outputs from this source. They receive a mean Attention Score of 2.9. This one has gotten more attention than average, scoring higher than 50% of its peers.
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