International Journal of Nanomedicine (Oct 2022)
ROS-Generating Poly(Ethylene Glycol)-Conjugated Fe3O4 Nanoparticles as Cancer-Targeting Sustained Release Carrier of Doxorubicin
Abstract
Boddu Adilakshmi,1 Obireddy Sreekanth Reddy,2– 4 Duddekunta Hemalatha,1 Kummari SV Krishna Rao,1 Wing-Fu Lai2,3 1Polymer Biomaterial Design and Synthesis Laboratory, Department of Chemistry, Yogi Vemana University, Kadapa, Andhra Pradesh, 516005, India; 2Department of Urology, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Zhejiang, 310012, People’s Republic of China; 3Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong Special Administrative Region, People’s Republic of China; 4Department of Chemistry, Sri Krishnadevaraya University, Anantapuramu, Andhra Pradesh, 515003, IndiaCorrespondence: Wing-Fu Lai; Kummari SV Krishna Rao, Email [email protected]; [email protected]: Site-specific drug delivery systems can contribute to the development and execution of effective cancer treatment. Due to its favorable features (including high biocompatibility, high hydrophilicity and ease of functionalization), poly(ethylene glycol) (PEG) has been widely adopted to design drug carriers. Generating carriers for delivery of hydrophobic anticancer agents, however, is still a challenge in carrier design.Methods: In the first step, PEG is functionalized with dialdehyde to generate PEG-(CHO)2 using EDC/NHS chemistry. In the second step, Fe3O4 nanoparticles are functionalized with amino groups to generate Fe3O4-NH2. In the third step, PEG-(CHO)2, Fe3O4-NH2 and doxorubicin (DOX) react in an acidic environment to yield a drug conjugate (PEGDA-MN-DOX), which is subsequently characterized by FT-IR, 1H-NMR, SEM, TEM, DLS, TGA, and DSC.Results: The chemical functionalities of the drug conjugate are confirmed by FTIR, H-NMRand XRD analysis.The release pattern of PEGDA-MN-DOX is investigated at 25 and 37 °C at different pH values. The results indicate that the developed drug conjugate cannot only behave as a sustained-release carrier, but can also generate a significant level of reactive oxygen species (ROS), leading to a high level of toxicity against MCF-7 cells while still showing excellent biocompatibility in 3T3 cells.Conclusion: The reported conjugate shows anticancer potential, cancer-targeting ability, and ROS-generating capacity for effective drug encapsulation and sustained release in chemotherapy.Graphical Abstarct: Keywords: PEG, doxorubicin, magnetic nanoparticles, anti-cancer, biocompatibility, drug delivery
