Herein, thermo-responsive liposomes (TLs) loaded with Asp (Asp/TLs) were produced by self-assembling DPPC, DSPE-PEG2000, and cholesterol. The preparation variables were optimized using the Box–Behnken design (BBD). The optimized Asp/TLs exhibited an average particle size of 114.05 ± 1.56 nm, PDI of 0.15 ± 0.015, zeta potential of −15.24 ± 0.65 mV, and entrapment efficiency (EE%) of 84.08 ± 2.75%. In addition, under physiological conditions, Asp/TLs showed spherical shape, outstanding stability and thermo-triggered the release of Asp at 38 °C, reaching the maximum Asp release at 40 °C. The MTT assay showed that the optimal Asp/TLs exhibited the highest cytotoxic activity upon exposure to mild hyperthermia (40 °C) against the invasive triple-negative breast cancer cell line (MDA-MB-231) when compared to other preparations. The IC₅₀ of Asp/TLs (40 °C) was estimated at 0.9 μg mL⁻¹, while that of free Asp (40 °C) was 3.83 μg mL⁻¹. As such, the optimal Asp/TLs were shown to increase the cytotoxic activity of Asp by 4-fold upon exposure to mild hyperthermia. The IC₅₀ values of Asp and Asp/TLs without exposure to 40 °C were 6.6 μg mL⁻¹ and 186 μg mL⁻¹, respectively. This indicated that Asp was released only when placed at 40 °C. The apoptosis assay revealed that Asp/TLs (40 °C) caused a remarkable increase in the percentage of cell population among both the late apoptosis and necrosis quartiles, as well as a significant decline in the viable cell quartile (P ≤ 0.001) when compared to Asp (40 °C). Asp/TLs (40 °C) and Asp (40 °C) could stimulate the intrinsic apoptosis pathway by upregulating the apoptotic genes Bak and Bax, while downregulating the anti-apoptotic genes, BCL-xL and BCL-2. The free Asp (40 °C) increased the gene expression of Bak and Bax by 4.4- and 5.2-folds, while reducing the expression of BCL-xL and BCL-2 by 50% and 73%, respectively. The optimal Asp TLs (40 °C) manifested more potent effects as demonstrated by the upregulation of Bak, Bax, and P53 by 5.6-, 7.2-, and 1.3-folds, as well as the downregulation of BCL-xL and BCL-2 by 70% and 85%, respectively. As such, the optimal Asp TLs (40 °C) treatment displayed the most potent cytotoxic profile and induced both apoptosis and necrosis in MDA-MB-231.

Smart pH-responsive niosomes loaded with either Oxaliplatin (Ox), Ylang ylang essential oil (Y-oil), or co-loaded with both compounds (Ox-Y) (Ox@NSs, Y@NSs, and Ox-Y@NSs, respectively) were formulated utilizing the thin film method. The developed nanocontainers had a spherical morphology with mean particle sizes lower than 170 nm and showed negative surface charges, high entrapment efficiencies, and a pH-dependent release over 24 h. The prepared pH-responsive niosomes’ cytotoxicity was tested against the invasive triple-negative breast cancer (MDA-MB-231) cells, compared to free OX and Y-oil. All niosomal formulations loaded with Ox and/or Y-oil significantly improved cytotoxic activity relative to their free counterparts. The Ox-Y@NSs demonstrated the lowest IC50 (0.0002 µg/mL) when compared to Ox@NSs (0.006 µg/mL) and Y@NSs (18.39 µg/mL) or unloaded Ox (0.05 µg/mL) and Y-oil (29.01 µg/mL). In addition, the percentages of the MDA-MB-231 cell population in the late apoptotic and necrotic quartiles were profoundly higher in cells treated with the smart Ox-Y@NSs (8.38% and 5.06%) than those exposed to free Ox (7.33% and 1.93%) or Y-oil (2.3% and 2.13%) treatments. Gene expression analysis and protein assays were performed to provide extra elucidation regarding the molecular mechanism by which the prepared pH-sensitive niosomes induce apoptosis. Ox-Y@NSs significantly induced the gene expression of the apoptotic markers Tp53, Bax, and Caspase-7, while downregulating the antiapoptotic Bcl2. As such, Ox-Y@NSs are shown to activate the intrinsic pathway of apoptosis. Moreover, the protein assay ascertained the apoptotic effects of Ox-Y@NSs, generating a 4-fold increase in the relative protein quantity of the late apoptotic marker Caspase-7. Our findings suggest that combining natural essential oil with synthetic platinum-based drugs in pH-responsive nanovesicles is a promising approach to breast cancer therapy.

Resveratrol, a naturally occurring polyphenol, has attracted significant attention due to its antioxidant, cardioprotective and anticancer potential. However, its low aqueous solubility limits resveratrol bioavailability and use. In this work, different mesoporous silica matrices were used to encapsulate the polyphenol and to increase its dissolution rate. Pristine MCM-41, MCM-48, SBA-15, SBA-16, FDU-12 and MCF silica were obtained. The influence of SBA-15 functionalized with aminopropyl, isocyanate, phenyl, mercaptopropyl, and propionic acid moieties on resveratrol loading and release profiles was also assessed. The cytotoxic effects were evaluated for mesoporous carriers and resveratrol-loaded samples against human lung cancer (A549), breast cancer (MDA-MB-231) and human skin fibroblast (HSF) cell lines. The effect on apoptosis and cell cycle were assayed for selected resveratrol-loaded carriers. The polyphenol molecules are encapsulated only inside the mesopores, mostly in amorphous state. All materials containing either pristine or functionalized silica carriers increased polyphenol dissolution rate. The influence of the physico-chemical properties of the mesoporous carriers and resveratrol–loaded supports on the kinetic parameters was identified. Resv@SBA-15-SH and Resv@SBA-15-NCO samples exhibited the highest anticancer effect against A549 cells (IC₅₀ values were 26.06 and 36.5 µg/mL, respectively) and against MDA-MB-231 (IC₅₀ values were 35.56 and 19.30 µg/mL, respectively), which highlights their potential use against cancer.

Combining sonochemistry with phytochemistry is a modern trend in the biosynthesis of metallic nanoparticles (NPs), which contributes to the sustainability of chemical processes and minimizes hazardous effects. Herein, titanium dioxide (TiO₂) NPs were bioengineered using a novel and facile ultrasound-assisted approach utilizing the greenly extracted essential oil of Ocimum basilicum. FTIR and UV-Vis spectrophotometry were used to confirm the formation of TiO₂ NPs. The X-ray diffraction (XRD) analysis showed the crystalline nature of TiO₂ NPs. TEM analysis revealed the spherical morphology of the NPs with sizes ranging from 5.55 to 13.89 nm. Energy-dispersive X-ray (EDX) confirmed the purity of the greenly synthesized NPs. TiO₂ NPs demonstrated outstanding antitumor activity against breast (MCF-7) and lung (A-549) cancer cells with estimated IC₅₀ values of 1.73 and 4.79 μg mL⁻¹. The TiO₂ NPs were cytocompatible to normal cells (MCF-10A) with a selectivity index (SI) of 8.77 for breast and 3.17 for lung cancer. Biological assays revealed a promising potential for TiO₂ NPs to induce apoptosis and arrest cells at the sub-G1 phase of the cell cycle phase in both cancer cell lines. Molecular investigations showed the ability of TiO₂ NPs to increase apoptotic genes' expression (Bak and Bax) and their profound ability to elevate the expression of apoptotic proteins (caspases 3 and 7). Molecular docking demonstrated strong binding interactions for TiO₂ NPs with caspase 3 and EGFR-TK targets. In conclusion, the greenly synthesized TiO₂ NPs exhibited potent antitumor activity and mitochondrion-based cell death against breast and lung cancer cell lines while maintaining cytocompatibility against normal cells.

Despite recent advancements in cancer therapies, challenges such as severe toxic effects, non-selective targeting, resistance to chemotherapy and radiotherapy, and recurrence of metastatic tumors persist. Consequently, there has been considerable effort to explore innovative anticancer compounds, particularly in immunotherapy, which offer the potential for enhanced biosafety and efficacy in cancer prevention and treatment. One such avenue of exploration involves the miRNA-34 (miR-34) family, known for its ability to inhibit tumorigenesis across various cancers. Dysregulation of miR-34 has been observed in several human cancers, and it is recognized as a tumor suppressor microRNA due to its synergistic interaction with the well-established tumor suppressor p53. However, challenges have arisen with the therapeutic application of miR-34a. These include its susceptibility to degradation by RNase in serum, limiting its ability to penetrate capillary endothelium and reach target cells, as well as reports of immunoreactive adverse reactions. Furthermore, unexpected side effects may occur, such as the accumulation of therapeutic miRNAs in healthy tissues due to interactions with serum proteins on nano-vector surfaces, nanoparticle breakdown in the bloodstream due to shearing stress, and unsuccessful extravasation of nanocarriers to target cells owing to interstitial fluid pressure. Despite these challenges, miR-34a remains a promising candidate for cancer therapy, and other members of the miR-34 family have also shown potential in inhibiting tumor cell proliferation. While the in vivo applications of miR-34b/c are limited, they warrant further exploration for oncotherapy. Recently, procedures utilizing nanoparticles have been developed to address the challenges associated with the clinical use of miR-34, demonstrating efficacy both in vitro and in vivo. This review highlights emerging trends in nanodelivery systems for miR-34 targeting cancer cells, offering insights into novel nanoformulations designed to enhance the anticancer therapeutic activity and targeting precision of miR-34. As far as current knowledge extends, no similar recent review comprehensively addresses the diverse nanoformulations aimed at optimizing the therapeutic potential of miR-34 in anticancer strategies.