<p>Cinnamaldehyde and Doxorubicin Co-Loaded Graphene Oxide Wrapped Mesoporous Silica Nanoparticles for Enhanced MCF-7 Cell Apoptosis</p>

Abstract

Background Combined chemotherapy is often affected by the different physicochemical properties of chemotherapeutic drugs, which should be improved by the reasonable design of co-loaded preparations. Purpose A kind of simple but practical graphene oxide (GO) wrapped mesoporous silica nanoparticles (MSN) modified with hyaluronic acid (MSN@GO-HA) were developed for the co-delivery of cinnamaldehyde (CA) and doxorubicin (DOX), in order to enhance their combined treatment on tumor cells and reduce their application defects. Methods The MSN CA @GO DOX -HA was constructed by MSN CA (loading CA via physical diffusion) and GO DOX -HA (modified with HA and loading DOX via π–π stacking) through the electrostatic adsorption, followed by the physicochemical characterization, serum stability and in vitro release study. Cytotoxicity on different cells was detected, followed by the tumor cell uptake tests. The intracellular reactive oxygen species (ROS) changes, mitochondrial functions and activities of caspase-3/-9 in MCF-7 cells were also evaluated, respectively. Results The MSN CA @GO DOX -HA nanoparticles kept stable in FBS solution and achieved pH-responsive release behavior, which was beneficial to increase the accumulation of CA and DOX in tumor cells to enhance the treatment. MSN CA @GO DOX -HA exerted higher cytotoxicity to MCF-7 human breast cancer cells than H9c2 cardiac myocyte cells, which were not only attributed to the active targeting to tumor cells by HA, but also related with the activation of intrinsic apoptotic pathway in MCF-7 cells induced by CA, which was mediated by the specific ROS signal amplification and the interference with mitochondrial function. Moreover, the efficacy of DOX was also enhanced by the above process. Conclusion The establishment of the MSN CA @GO DOX -HA nanoparticles played a role in promoting strengths and restricting shortcomings of CA and DOX, thereby exerting their function and achieving efficient treatment against cancer.

The Therapeutic Roles of Cinnamaldehyde against Cardiovascular Diseases

“…Zhao et al suggested that CA encapsulated in submicrometer emulsions exhibited higher plasma concentration, faster tissue distribution, and better antitumor effects in rats when compared to CA alone [ 32 ]. Similarly, Dong et al reported that nanogel packaging of CA enabled the controlled release and oxidation inhibition of drug and oxidation inhibition, which consequently increased CA's bioavailability and more effectively promoted cancer cell apoptosis [ 53 ]. With the advancement in molecular biology, a large number of bioactive substances, including dextran, silica, chitosan, cyclodextrin, and hyaluronic acid, have been found to synthesize carriers for improving the therapeutic efficacy of CA [ 46 , 48 , 51 , 53 , 60 ].…”

Nano-drug co-delivery system of natural active ingredients and chemotherapy drugs for cancer treatment: a review

“…Dong et al. ( 2020 ) developed mesoporous silica nanoparticles ( Figure 6 ) coated with graphene oxide modified by HA for the combined administration of CA and DOX to enhance their combined therapeutic effect on tumor cells. CA and DOX co-loaded graphene oxide coated mesoporous silica nanoparticles (MSNCA @ GODOX-HA) actively targeted tumor cells through the “ligand receptor” affinity between HA and CD44 receptors, improved the advantages of CA and DOX, limited their shortcomings, so as to achieve effective treatment of cancer.…”

Dual CEA/CD44 targeting to colorectal cancer cells using nanobody-conjugated hyaluronic acid-modified mesoporous silica nanoparticles with pH- and redox-sensitivity

“…DOX was employed as the fluorescent probe as it emits red fluorescence under a specified wavelength of excitation light. 41,42 The cell nuclei were stained in blue by DAPI since it is a fluorescent dye that binds strongly to DNA. As shown in Fig.…”