Doxorubicin-Conjugated Zinc Oxide Nanoparticles, Biogenically Synthesised Using a Fungus Aspergillus niger, Exhibit High Therapeutic Efficacy against Lung Cancer Cells

Abstract

This study reports the therapeutic effectiveness of doxorubicin-conjugated zinc oxide nanoparticles against lung cancer cell line. The zinc oxide nanoparticles (ZnONPs) were first synthesised using a fungus, isolated from air with an extraordinary capability to survive in very high concentrations of zinc salt. Molecular analysis based on 18S rRNA gene sequencing led to its identification as Aspergillus niger with the NCBI accession no. OL636020. The fungus was found to produce ZnONPs via the reduction of zinc ions from zinc sulphate. The ZnONPs were characterised by various biophysical techniques. ZnONPs were further bioconjugated with the anti-cancer drug doxorubicin (DOX), which was further confirmed by different physical techniques. Furthermore, we examined the cytotoxic efficacy of Doxorubicin-bioconjugated-ZnONPs (DOX-ZnONPs) against lung cancer A549 cells in comparison to ZnONPs and DOX alone. The cytotoxicity caused due to ZnONPs, DOX and DOX-ZnONPs in lung cancer A549 cells was assessed by MTT assay. DOX-ZnONPs strongly inhibited the proliferation of A549 with IC50 value of 0.34 μg/mL, which is lower than IC50 of DOX alone (0.56 μg/mL). Moreover, DOX-ZnONPs treated cells also showed increased nuclear condensation, enhanced ROS generation in cytosol and reduced mitochondrial membrane potential. To investigate the induction of apoptosis, caspase-3 activity was measured in all the treated groups. Conclusively, results of our study have established that DOX-ZnONPs have strong therapeutic efficacy to inhibit the growth of lung cancer cells in comparison to DOX alone. Our study also offers substantial evidence for the biogenically synthesised zinc oxide nanoparticle as a promising candidate for a drug delivery system.

Scaling-up strategies for controllable biosynthetic ZnO NPs using cell free-extract of endophytic Streptomyces albus: characterization, statistical optimization, and biomedical activities evaluation

“…This white color is common for ZnO NPs, which are equivalent to earlier biosynthetic ZnO NPs generated from other bioactive materials and have a visible range of 300-400 nm 51 . The real highest absorption peak of synthetic ZnO NPs that verified the generation of ZnO NPs previously ranged from 275 to 365 nm, depending on the biosynthesis technique and reduction reaction (reductant and precursor) utilized 20,33,[52][53][54][55] . For our biosynthetic ZnO NPs, the maximum UV-visible absorption peak was found at 320 nm.…”

“…The antimicrobial capabilities of NPs were influenced by their size, shape, concentration, surface area-tomass ratio, and physico-chemical properties. For example, the size of NPs and their antimicrobial properties are inversely correlated; as the particle size decreased, the inhibitory effect increased 52 . Tiny NPs quickly interacted with the cell surface due to their increased surface reactivity, breaking the cell membrane and causing intracellular component leakage and cell death 33 .…”

PMO/ZnO nanocomposites as nanocarriers for gemcitabine release

“…The studies have also demonstrated that ZnO nanoparticles can be used as drug delivery systems with controlled release of anticancer drugs. Finally, pH-sensitive Zinc Oxide nanoparticles have been shown to release anticancer drugs like cisplatin in a controllable manner [10][11][12]. In recent years, essential attention has been given to the green synthesis of nanoparticles because it is an eco-friendly method and the non-use of fewer chemical compounds can also have a signi cant impact on the biological properties of materials [13][14][15] In 1999, three research groups independently created mesoporous organosilica compounds from organic bipolar alkoxysilane precursors.…”

Design and Evaluation of Periodic Mesoporous Organosilica/ZnO Nanocomposites as an Effective Drug Delivery System for Gemcitabine

“…In the following, some research studies are mentioned that have investigated the use of ZnO in cancer. Mishra et al [10] reported in their study about the therapeutic effectiveness of doxorubicinconjugated zinc oxide nanoparticles against lung cancer cell lines. Results show that, in comparison to anticancer drugs alone, the compounds ZnO and doxorubicin have strong therapeutic e cacy to inhibit the growth of lung cancer cells.…”