Anti-EGFR anchored paclitaxel loaded PLGA nanoparticles for the treatment of triple negative breast cancer. In-vitro and in-vivo anticancer activities

• Published in: PloS one 2018-11, Vol.13 (11), p.e0206109-e0206109
• Main Authors: Venugopal, Vijayan, Krishnan, Shalini, Palanimuthu, Vasanth Raj, Sankarankutty, Subin, Kalaimani, Jayaraja Kumar, Karupiah, Sundram, Kit, Ng Siew, Hock, Tang Thean
• Format: Article
• Language: English
• Subjects: Accumulation; Animals; Anticancer properties; Antitumor activity; Biocompatibility; Biology and Life Sciences; Breast cancer; Cancer; Cancer therapies; Cell cycle; Cell Line, Tumor; Cell Survival - drug effects; Chemotherapy; Computing time; Cytotoxicity; Delayed-Action Preparations; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug delivery systems; Engineering and Technology; Entrapment; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - chemistry; Gel electrophoresis; Humans; Medical prognosis; Medical research; Medicine and Health Sciences; Mice; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - chemistry; Pharmaceutical sciences; Pharmacy; Physical Sciences; Plasma; Polylactic Acid-Polyglycolic Acid Copolymer; Polylactide-co-glycolide; Proteins; Research and Analysis Methods; Side effects; Sodium lauryl sulfate; Toxicity; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - pathology; Tumors; Xenograft Model Antitumor Assays
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0206109

The aim of the present study is to analyze the viability of anti-EGFR anchored immunonanoparticle (INP) bearing Paclitaxel (PTX) to specifically bind the EGFR protein on the TNBC cells. The NP was prepared by nanoprecipitation and characterized the particle size, charge, entrapment of drug and release of it. The anti-EGFR anchored and the integrity was confirmed by SDS-PAGE. Cytotoxicity and NPs cellular uptake was analyzed with MDA-MB-468 type cancer cells and the EGFR expression was confirmed by PCR, qualitatively and quantitatively. The in-vivo antitumor activity of INP was determined by using athymic mice model and targeting efficiency was measured by calculating the PTX accumulation in the tumor plasma. The prepared INP with the size of 336.3 nm and the charge of -3.48 mV showed sustained drug release upto 48 h. The INP showed significant reduction of cancer cell viability of 10.6% for 48 h with 93 fold higher PTX accumulation in the tumor plasma compared with NPs. Based on these reports, we recommend that anti-EGFR anchored PTX loaded NP may have the ability to target the TNBC cells and improve the therapeutic action and subsidize the side effects of PTX for the treatment of TNBC.