Zenli Cheng
1* 
, Ashok Kumar Janakiraman
1* , Baskaran Gunasekaran
2 , Crystale Lim Siew Ying
2 , Ezanee Azlina Binti Mohamad Hanif
3 , Hanish Singh Jayasingh Chellammal
4 , Sinouvassane Djearamane
5 1 Faculty of Pharmaceutical Sciences, UCSI University, 56000 Cheras, Kuala Lumpur, Malaysia.
2 Faculty of Applied Sciences, UCSI University, 56000 Cheras, Kuala Lumpur, Malaysia.
3 UKM Medical Molecular Biology Institute, University Kebangsaan Malaysia, Malaysia.
4 Faculty of Pharmacy, University Teknologi Mara, 40450 Shah Alam, Selangor, Malaysia.
5 Faculty of Science, University Tunku Abdul Rahman, 31900 Kampar, Perak, Malaysia.
Abstract
Zinc oxide nanoparticles (ZnO-NPs) in their many formulations have prompted an immense interest in nanomedicine and drug development. Numerous ZnO-NPs bioactive formulations demonstrate remarkable broad applications in deciphering their therapeutic effects and bioimaging. Their unique size, morphology-dependent properties and modifiable surface chemistry have made them promising candidates for translation into novel, alternative nanomedicines. ZnO-NPs demonstrate biocompatibility and are non-toxic with relatively required in-expensive production techniques. This review presents an in-depth comprehension of the synthesis, chemical and biological peculiarities of ZnO-NPs, including their varied manufacturing methods and their impactful applications in biomedicine. The physical, chemical and biological synthesis approaches that are unique for ZnO-NPs synthesis were comprehensively reviewed, followed by their applications in therapeutics (anticancer, antibacterial, drug delivery, skin treatment, antidiabetic and antioxidant), diagnostics (bioimaging and biosensor) and theranostics as well as their health hazards. ZnO-NPs exhibit antibacterial and anticancer activities, primarily through the liberation of zinc ions and generation of reactive oxygen species (ROS), which disrupt the cell membrane. Their anticancer properties are additionally apprised with an escalation in caspase 3/7 along with the modulation of pro- and anti-apoptotic proteins. ZnO-NPs are reviewed to attenuate hepatocellular carcinoma. Further, this article comprehended various in-vitro and in-vivo therapeutic effects of novel drug formulations of ZnO-NPs. It also delved into two fascinating areas: ZnO-NPs’ performance in comparison with other NPs and the potential of ZnO-NPs heterostructures with 2D nanomaterials. The goal of this review is to inspire further research efforts to meet the growing needs of next-generation nanomedicine.