<p>CD-340 functionalized doxorubicin-loaded nanoparticle induces apoptosis and reduces tumor volume along with drug-related cardiotoxicity in mice</p>
Authors: Raghuvir H Gaonkar
Laboni Mondal
Sanchari Bhattacharya
Biswajit Mukherjee
Debasmita Dutta
Murari Mohan Pal
Shreyasi Chakraborty
Kaushik Das
Mita Chatterjee Debnath
Journal: International Journal of Nanomedicine (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: breast cancer; ligand; nanoparticles; targeting; tumor.
Affiliations: Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India., Department of Biological Chemistry, Indian Association for the Cultivation of Science, Kolkata 700032, India., Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700032, India.

Abstract:  Background and objective: Targeted drug delivery of nanoparticles decorated with site-specific recognition ligands is of considerable interest to minimize cytotoxicity of chemotherapeutics in the normal cells. The study was designed to develop CD-340 antibody-conjugated polylactic-co-glycolic acid (PLGA) nanoparticles loaded with a highly water-soluble potent anticancer drug, doxorubicin (DOX), to specifically deliver entrapped DOX to breast cancer cells. Methods: The study showed how to incorporate water-soluble drug in a hydrophobic PLGA (85:15) based matrix which otherwise shows poor drug loading due to leaching effect. The optimized formulation was covalently conjugated to anti-human epidermal growth factor receptor-2 (HER2) antibody (CD-340). Surface conjugation of the ligand was assessed by flow cytometry, confocal microscopy, and gel electrophoresis. Selectivity and cytotoxicity of the experimental nanoparticles were tested on human breast cancer cells SKBR-3, MCF-7, and MDA-MB-231. Both CD-340-conjugated and unconjugated nanoparticles were undergone in vitro and in vivo characterization. Result: Higher level of incorporation of DOX (8.5% W/W), which otherwise shows poor drug loading due to leaching effect of the highly water-soluble drug, was seen in this method. In HER2-overexpressing tumor xenograft model, radiolabeled antibody-conjugated nanoparticles showed preferentially more of the formulation accumulation in the tumor area when compared to the treatments with the unconjugated one or with the other control groups of mice. The ligand conjugated nanoparticles showed considerable potential in reduction of tumor growth and cardiac toxicity of DOX in mice, a prominent side-effect of the drug. Conclusion: In conclusion, CD-340-conjugated PLGA nanoparticles containing DOX preferentially delivered encapsulated drug to the breast cancer cells and in breast tumor and reduced the breast tumor cells by apoptosis. Site-specific delivery of the formulation to neoplastic cells did not affect normal cells and showed a drastic reduction of DOX-related cardiotoxicity. 

Retracted: No

PubPeer comments:
 This paper has a November 2019 correction found here: https: www.dovepress.com corrigendum-cd-340-functionalized-doxorubicin-loaded-nanoparticle-indu-peer-reviewed-fulltext-article-IJN It reads:  Upon reviewing the published article, the authors noticed a few errors that they had overlooked while completing their revisions. (...) Upon reviewing the published article, the authors noticed a few errors that they had overlooked while completing their revisions. * On page 8082, in Figure 2. The label of X-axis u201cTime (Days)u201d should be replaced with u201cTime (hrs)u201d. The corrected Figure 2 is below. *On page 8087, in the right column under the sub-heading u201cIn vivo cardiac toxicity studyu201d 2nd paragraph, 2nd line: u201cu2026LV fractional shorteningu2026u201d should read u201cu2026R-R intervalu2026u201d. * On page 8089, in the legend section of Figure 9, under u201cNote: (A)u201d the word u201cEchocardiographyu201d should be replaced with u201cElectrocardiographyu201d On page, 8092 left column, 1st paragraph, first line, u201cechocardiogramu201d should be u201celectrocardiogramu201d. On page 8092, under the heading u201cAcknowledgementu201d in the 2nd paragraph, last line, the word u201cEchocardiographyu201d should be replaced with u201cElectrocardiographyu201d. On page 8092, in the u201cAcknowledgementu201d section, Dr. Sanmoy Karmakar and Rudranil Bhowmik request to be removed from this section. The section should be replaced with u201cAuthors are indebted to the Indian Council of Medical Research for providing the financial grant (Ref No 45 6 2013Nan BMS dated 24.02.2015) and Doctoral Scholarship under RUSA 2.0 Scheme (Ref No R-11 144 19 dated 25 02 2019) to conduct the study.u201d , 
 Could the authors also please check Figure 5? * Orange boxes: In thee 6h panels, the bright field DOX-Ab-NP and DOX-NP panels in the MDA MB231 rows appear to look the same.  , 
 A second Corrigendum, from February 2021, can now be found here: https: www.dovepress.com corrigendum1-cd-340-functionalized-doxorubicin-loaded-nanoparticle-ind-peer-reviewed-fulltext-article-IJN  The authors have advised due to an error at the time of figure assembly, Figure 5 on page 8085 is incorrect. The correct Figure 5 is shown below. The authors apologize for this error and advise it does not affect the results of the paper. ,