CD-340 functionalized doxorubicin-loaded nanoparticle induces apoptosis and reduces tumor volume along with drug-related cardiotoxicity in mice

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.

Keywords:

• breast cancer
• nanoparticles
• ligand
• targeting
• tumor

View correction statement:

CD-340 Functionalized Doxorubicin-Loaded Nanoparticle Induces Apoptosis and Reduces Tumor Volume Along with Drug-Related Cardiotoxicity in Mice [Corrigendum]

CD-340 Functionalized Doxorubicin-Loaded Nanoparticle Induces Apoptosis And Reduces Tumor Volume Along With Drug-Related Cardiotoxicity In Mice [Corrigendum]

Acknowledgment

Authors 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.

The authors acknowledge Dr. Sanmoy Karmakar and Rudranil Bhowmik for helping in technical issues related to the Echocardiography study in mice.

Ethical conduct of research

The experimental protocol of the study was approved by the Institutional Animal Ethics Committee of Jadavpur University, Kolkata. Animal care was in accordance with the Committee for the Purpose of Control and Supervision of Experiments on Animals guidelines.

Disclosure

The authors of this article have no conflict of interest to declare with regard to this work.