One-pot synthesis and enzyme-responsiveness of amphiphilic doxorubicin prodrug nanomicelles for cancer therapeutics

• Published in: RSC advances Vol. 12; no. 43; pp. 27963 - 27969
• Main Authors: Han, Ling-Na, Wang, Kai-Qiang, Ren, Zi-Ning, Yang, Xue, Duan, Xiao, Krishnan, Sasirekha, Jaisankar, Abinaya, Park, Jeong-Hui, Dashnyam, Khandmaa, Zhang, Wujie, Pedraz, José Luis, Ramakrishna, Seeram, Kim, Hae-Won, Li, Chang-Feng, Song, Li-Hua, Ramalingam, Murugan
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 28.09.2022; The Royal Society of Chemistry
• Subjects: Cancer; Chemistry; Doxorubicin; Enzymes; Esterification; Fourier transforms; Glutamic acid; NMR; Nuclear magnetic resonance; Nuclear reactions; Polyethylene glycol; Spectrophotometry; Synthesis
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d2ra04436f

In this study, we report a one-pot synthesis and enzyme-responsiveness of polyethylene glycol (PEG) and glutamic acid (Glu)-based amphiphilic doxorubicin (DOX) prodrug nanomicelles for cancer therapeutics. The nanomicelles were accomplished by esterification and amidation reactions. The nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) data confirmed the structure of nanomicelles. The DOX-loaded nanomicelles showed a DLS-measured average size of 107 nm and excellent stability in phosphate-buffered saline (PBS) for 7 days. The drug loading and cumulative release rates were measured by ultraviolet-visible (UV-vis) spectrophotometry at 481 nm. The cumulative release rate could reach 100% in an enzyme-rich environment. Further, the therapeutic efficiency of nanomicelles to cancer cells was determined by cell viability and cellular uptake and distribution using HeLa cells. The cell viability study showed that the DOX-loaded nanomicelles could effectively inhibit the HeLa cell proliferation. The cellular uptake study confirmed that the nanomicelles could be effectively ingested by HeLa cells and distributed into cell nuclei. Based on the collective experimental data, this study demonstrated that the synthesized nanomicellar prodrug of DOX is a potential candidate for cancer therapeutics. A doxorubicin-based nanomedicine with a one-pot synthesis method and FDA-approved materials could solve the problems of a complicated preparation process and avoid the use of non-FDA-approved materials for clinical use and industrial production.