Co-Delivery of Ylang Ylang Oil of Cananga odorata and Oxaliplatin Using Intelligent pH-Sensitive Lipid-Based Nanovesicles for the Effective Treatment of Triple-Negative Breast Cancer

Abstract

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.

PEGylated Chitosan Nanoparticles Loaded with Betaine and Nedaplatin Hamper Breast Cancer: In Vitro and In Vivo Studies

“…Therefore, nanoformulation of chemotherapeutics could improve their physicochemical properties and reduce their systematic side effects. 3 Additionally, investigating the molecular mechanisms involved in BC's malignant transformation and metastasis would shed light on key molecules that could be targeted for its prevention. 4−7 Platinum-based chemotherapies are still the standard first-line chemotherapy regimen for many solid tumors, including BC.…”

Newly Synthesized Anticancer Purine Derivatives Inhibiting p-EIF4E Using Surface-Modified Lipid Nanovesicles

“…Chitosan is a biocompatible and biodegradable natural polymer with mucoadhesive properties. This would lead to the adhesion of the niosomes to the cancer cell membrane, prolong the residence time of the niosomes at the site of action, and achieve a controlled release of the payload at cancer cells . Thus, to exploit the benefits of loading anticancer drugs in chitosan-coated niosomes (Cs/NSs), compound 4b was loaded into Cs/NSs, forming Cs/ 4b -NSs.…”

“…This is attributed to the presence of the cationic amino groups of chitosan on the surface, which shield the negative charges of the niosomes. These findings proved the successful coating of niosomes with chitosan . The outstanding positive charge on the surface of Cs/ 4b -NSs hinders the clumping of the niosomal formulation upon storage.…”

Box–Behnken design of thermo-responsive nano-liposomes loaded with a platinum(iv) anticancer complex: evaluation of cytotoxicity and apoptotic pathways in triple negative breast cancer cells

“…Lastly, the stained cells were analyzed using ACEA 2 uorescent channels Novocyte™ ow cytometer (ACEA Biosciences Inc., San Diego, CA, USA), and quadrant analysis was performed as described previously. 36 2.8.7. Gene expression analysis.…”