Chemotherapy is a vital option for cancer treatment; however, its therapeutic outcomes are limited by dose-dependent toxicity and the occurrence of chemoresistance. siRNAs have emerged as an attractive therapeutic option enabling specific interference with target genes. Combination therapy using chemotherapeutic agents along with gene therapy could be a potential strategy for cancer management, which not only improves therapeutic efficacy but also decreases untoward effects from dose reduction. In this study, a cationic niosome containing plier-like cationic lipid B was used to convey siRNA against anti-apoptotic mRNA into MCF-7 and MDA-MB-231 cells. Mcl-1 silencing markedly decreased the viability of MCF-7 cells and triggered apoptosis. Moreover, computer modeling suggested that the combination of doxorubicin (Dox) and Mcl-1 siRNA exhibited a synergistic relationship and enabled a dose reduction of each agent at 1.71 and 3.91 folds, respectively, to reach a 90% inhibitory effect when compared to single-agent treatments. Synergistic antitumor activity was further verified in a 3D spheroid culture which revealed, in contrast to single-agent treatment, the combination markedly decreased spheroid volume over time. Together, the combination therapy between Mcl-1 silencing and Dox exhibits a synergistic effect that may be exploited for novel breast cancer treatment.

Breast cancer is the second leading cause of cancer-related death in the US. However, recurrence is frequently found despite adjuvant therapy being available. Combination therapy with cytotoxic drugs and gene therapy is being developed to be a new promising cancer treatment strategy. Introducing substituted dithiocarbamate moieties at the C12 position of andrographolide (3nAG) could improve its anticancer selectivity in the MCF-7 breast cancer cell line. However, its hydrophobicity is one of its main drawbacks. This work successfully prepared 3nAG nanosuspension stabilized with the chitosan derivative NSC (3nAGN-NSC) to increase solubility and pharmacological effectiveness. siRNAs have emerged as a promising therapeutic alternative for interfering with particular mRNA. The 3nAGN-NSC had also induced Mcl-1 mRNA expression in MCF-7 human breast cancer cells at 8, 12, and 24 h. This indicates that, in addition to Mcl-1 silencing by siRNA (siMcl-1) in MCF-7 with substantial Mcl-1 reliance, rationally devised combination treatment may cause the death of cancer cells in breast cancer. The Fa-CI analysis showed that the combination of 3nAGN-NSC and siMcl-1 had a synergistic effect with a combination index (CI) value of 0.75 (CI < 1 indicating synergistic effects) at the fractional inhibition of Fa 0.7. The synergistic effect was validated by flow cytometry, with the induction of apoptosis as the mechanism of reduced cell viability. Our findings suggested the rational use of 3nAGN-NSC in combination with siMcl-1 to kill breast cancer cells.

Carbon-based nanoparticles (CNPs) have gained recognition because of their good biocompatibility, easy preparation, and excellent phototherapy properties. In biomedicine applications, CNPs are widely applied as photodynamic agents for antibacterial purposes. Photodynamic therapy has been considered a candidate for antibacterial agents because of its noninvasiveness and minimal side effects, especially in the improvement in antibacterial activity against multidrug-resistant bacteria, compared with conventional antibiotic medicines. Here, we developed CNPs from an active polyhydroxy phenolic compound, namely, gallic acid, which has abundant hydroxyl groups that can yield photodynamic effects. Gallic acid CNPs (GACNPs) were rapidly fabricated via a microwave-assisted technique at 200 °C for 20 min. GACNPs revealed notable antibacterial properties against Gram-positive and Gram-negative bacteria, including Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli). The minimum inhibitory concentrations of GACNPs in S. aureus and E. coli were equal at approximately 0.29 mg/mL and considerably lower than those in gallic acid solution. Furthermore, the GACNP-loaded hydrogel patches demonstrated an attractive photodynamic effect against S. aureus, and it was superior to that of Ag hydrofiber^®, a commercial material. Therefore, the photodynamic properties of GACNPs can be potentially used in the development of antibacterial hydrogels for wound healing applications.

The challenge in HER2-overexpressing breast cancer therapy lies in creating an effective target therapy to overcome treatment resistance. Monoclonal antibodies and target gene silencing by siRNA are two potential strategies that have been widely developed for treating HER2-positive breast cancer. The siRNA delivery system is a crucial factor that influences siRNA therapy’s success. In this study, lipid-based nanoparticles (cationic niosomes) composed of different cholesterol-based cationic lipids were formulated and characterized for delivering siRNA into HER2-overexpressing breast cancer cells. Niosomes containing a trimethylammonium headgroup showed the highest siRNA delivery efficiency with low toxicity. The myeloid cell leukemia-1 (Mcl-1) siRNA nioplex treatment significantly decreased mRNA expression and breast cancer cell growth. Dual-targeted therapy, consisting of treatment with an Mcl-1 siRNA nioplex and trastuzumab (TZ) solution, noticeably promoted cell-growth inhibition and apoptosis. The synergistic effect of dual therapy was also demonstrated by computer modeling software (CompuSyn version 1.0). These findings suggest that the developed cationic niosomes were effective nanocarriers for siRNA delivery in breast cancer cells. Furthermore, the Mcl-1 nioplex/TZ dual treatment establishes a synergistic outcome that may have the potential to treat HER2-overexpressing breast cancer.

Currently, fused deposition modeling (FDM) is a 3D printing technology that has been most widely used to develop innovative drug delivery approaches for overcoming the limitations of oral drug administration. Propranolol has a short plasma half-life and is well soluble in acidic environments. Thus, this study aimed to develop a gastro-floating 3D printed device (GFD) to sustain the release of propranolol in the stomach as a gastro-retentive drug delivery system. The polylactic acid (PLA) was selected to fabricate the GFD. An air chamber was included in the interior construction of the GFD design for buoyancy. The number of open channels on the side wall of GFD was modified to regulate release. The propranolol gel formulation was composed of a mixture of propranolol and polyvinylpyrrolidone (PVP) at the weight ratio of 6:5 and was then loaded into GFDs using a syringe. GFD exhibited a floating ability of more than 24 h with low standard deviation (SD) values of weight variation and shape dimension. The propranolol release from GFD shows sustained release properties in the simulated gastric environment without lag time. The 4 and 5 channels of GFD exhibited sustained drug release for 6 h. In addition, the duration of sustained release for 8 h was achieved from the GFD with 2 and 3 channels. The kinetic release of propranolol from GFDs was the best fit with zero-order. Thus, the GFDs could be designed to control the drug release according to each patient, which has the potential for applying personalized gastro-retentive drug delivery in various medications. Graphical abstract