| Title |
Investigation of antitumor activities of trastuzumab delivered by PLGA nanoparticles
|
|---|---|
| Published in |
International Journal of Nanomedicine, February 2018
|
| DOI | 10.2147/ijn.s152742 |
| Pubmed ID | |
| Authors |
Barbara Colzani, Laura Pandolfi, Ada Hoti, Pietro Alessandro Iovene, Antonino Natalello, Svetlana Avvakumova, Miriam Colombo, Davide Prosperi |
| Abstract |
We report the development of an efficient antibody delivery system for the incorporation of trastuzumab (TZ) into poly(lactic-co-glycolic) acid nanoparticles (PLGA NPs). The aim of the work was to overcome the current limitations in the clinical use of therapeutic antibodies, including immunogenicity, poor pharmacokinetics, low tumor penetration and safety issues. Trastuzumab-loaded PLGA NPs (PLGA-TZ) were synthesized according to a double emulsion method. The same protocol was used to produce control batches of nonspecific IgG-loaded NPs and empty PLGA NPs. After release of TZ from PLGA NPs, the effects on the main biological activities of the antibody were evaluated on SKBR3 (human epidermal growth factor receptor 2 [HER2]-positive breast cancer cell line), including specific binding to HER2, phosphorylation of HER2 (Y1248), degradation of HER2 protein and antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. In addition, an MTT assay was performed for treating SKBR3 cells with PLGA NPs loaded with TZ and doxorubicin to evaluate the cytotoxic activity of the combined treatment. TZ was gradually released in a prolonged way over 30 days. The physical characterization performed with circular dichroism, Fourier transform infrared and fluorescence spectroscopy of TZ after release demonstrated that no structural alterations occurred compared to the native antibody. In vitro experiments using SKBR3 cells showed that TZ released from PLGA NPs maintained the same biological activity of native TZ. PLGA NPs allowed a good co-encapsulation efficiency of TZ and doxorubicin resulting in improved therapy. With the TZ case study, we demonstrate that the distinctive features of therapeutic monoclonal antibodies, including molecular targeting efficiency, capability to inhibit or properly affect the regulatory signaling pathways of cancer cells and stimulation of the ADCC, are fully preserved after loading into and release from PLGA NPs. In addition, PLGA NPs are shown to allow for the simultaneous incorporation of TZ and conventional chemotherapeutics, resulting in a potent antitumor nanodrug well suited for in situ combination and neoadjuvant therapy. |
X Demographics
The data shown below were collected from the profiles of 11 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Italy | 7 | 64% |
| Canada | 1 | 9% |
| Germany | 1 | 9% |
| Unknown | 2 | 18% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 8 | 73% |
| Scientists | 3 | 27% |
Mendeley readers
The data shown below were compiled from readership statistics for 90 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 90 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 16 | 18% |
| Researcher | 9 | 10% |
| Student > Master | 9 | 10% |
| Student > Doctoral Student | 8 | 9% |
| Student > Bachelor | 5 | 6% |
| Other | 12 | 13% |
| Unknown | 31 | 34% |
| Readers by discipline | Count | As % |
|---|---|---|
| Pharmacology, Toxicology and Pharmaceutical Science | 14 | 16% |
| Biochemistry, Genetics and Molecular Biology | 11 | 12% |
| Medicine and Dentistry | 7 | 8% |
| Chemistry | 5 | 6% |
| Engineering | 4 | 4% |
| Other | 12 | 13% |
| Unknown | 37 | 41% |
Attention Score in Context
This research output has an Altmetric Attention Score of 7. 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 06 March 2018.
All research outputs
#5,190,504
of 25,382,440 outputs
Outputs from International Journal of Nanomedicine
#471
of 4,122 outputs
Outputs of similar age
#106,752
of 448,849 outputs
Outputs of similar age from International Journal of Nanomedicine
#8
of 83 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. Compared to these this one has done well and is in the 79th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,122 research outputs from this source. They receive a mean Attention Score of 4.7. This one has done well, scoring higher than 88% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 448,849 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 76% of its contemporaries.
We're also able to compare this research output to 83 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 90% of its contemporaries.