Herceptin-functionalized pure paclitaxel nanocrystals for enhanced delivery to HER2-postive breast cancer cells

• Published in: International journal of pharmaceutics 2016-11, Vol.513 (1-2), p.543-553
• Main Authors: Noh, Jin-Ki, Naeem, Muhammad, Cao, Jiafu, Lee, Eun Hee, Kim, Min-Soo, Jung, Yunjin, Yoo, Jin-Wook
• Format: Article
• Language: English
• Subjects: Adsorption; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Breast Neoplasms; Cell Cycle - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Drug Delivery Systems; Drug Liberation; HER2-positve breast cancer; Herceptin; Humans; Nanocrystals; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Paclitaxel; Paclitaxel - administration & dosage; Paclitaxel - chemistry; Particle Size; Receptor, ErbB-2; Trastuzumab - administration & dosage; Trastuzumab - chemistry; Tumor-targeting
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2016.09.067

[Display omitted] The objective of this study was to prepare Herceptin (HCT)-functionalized paclitaxel nanocrystals and evaluated their cell-specific interactions, cellular accumulation, and growth inhibition in HER2-positve breast cancer cells as a tumor-targeted delivery module. Paclitaxel (PTX) was fabricated in the form of nanocrystals (PNCs) by a sono-precipitation method, and HCT were coated using a facile non-covalent method (PNCs-HCT). Our results showed that the PNCs-HCT were stable for at least 1month at 4°C with no noticeable desorption of HCT. The release test showed that PNCs-HCT exhibited sustained drug release similar to only PNCs but with a higher release rate than only PTX powder. Cellular uptake, cytotoxicity, and cell cycle arrest studies revealed that PNCs-HCT exhibit greater binding affinity and higher cell-specific internalization to HER2-positive breast cancer cell lines as compared to PNCs, followed by enhanced cell growth inhibition. HCT-functionalized PNCs presented in this study offer a promising strategy for targeted pure drug nanocrystal delivery and enhancing the efficiency of anticancer therapy.