Co-Delivery of Letrozole and Cyclophosphamide via Folic Acid-Decorated Nanoniosomes for Breast Cancer Therapy: Synergic Effect, Augmentation of Cytotoxicity, and Apoptosis Gene Expression

Abstract

Breast cancer is one of the most prevalent causes of cancer mortality in women. In order to increase patient prognosis and survival rates, new technologies are urgently required to deliver therapeutics in a more effective and efficient manner. Niosome nanoparticles have been recently employed as therapeutic platforms capable of loading and carrying drugs within their core for both mono and combination therapy. Here, niosome-based nanoscale carriers were investigated as a targeted delivery system for breast cancer therapy. The platform developed consists of niosomes loaded with letrozole and cyclophosphamide (NLC) and surface-functionalized with a folic-acid-targeting moiety (NLCPFA). Drug release from the formulated particles exhibited pH-sensitive properties in which the niosome showed low and high release in physiological and cancerous conditions, respectively. The results revealed a synergic effect in cytotoxicity by co-loading letrozole and cyclophosphamide with an efficacy increment in NLCPFA use in comparison with NLC. The NLCPFA resulted in the greatest drug internalization compared to the non-targeted formulation and the free drug. Additionally, downregulation of cyclin-D, cyclin-E, MMP-2, and MMP-9 and upregulating the expression of caspase-3 and caspase-9 genes were observed more prominently in the nanoformulation (particularly for NLCPFA) compared to the free drug. This exciting data indicated that niosome-based nanocarriers containing letrozole and cyclophosphamide with controlled release could be a promising platform for drug delivery with potential in breast cancer therapy.

Formulation and Characterization of Poly (Ethylene Glycol)-Coated Core-Shell Methionine Magnetic Nanoparticles as a Carrier for Naproxen Delivery: Growth Inhibition of Cancer Cells

“…After a 24 h incubation period, suspensions of various samples (0–35 µg/mL) were added to the medium and incubated for another 24 h period as well as for 48 and 72 h. In the next step, the contents of the 96-well plates were replaced by the MTT solution in each well after another 4 h of incubation at 37 °C in a 5% CO 2 environment. To dissolve the purple formazan crystals, the medium was replaced and added to each well with 0.05 mL of dimethyl sulfoxide (DMSO) [ 39 , 40 ]. Finally, the absorbance of each well was measured using a microplate reader at 570 nm.…”

Folate-Targeted Curcumin-Loaded Niosomes for Site-Specific Delivery in Breast Cancer Treatment: In Silico and In Vitro Study

“…Cur has the capacity to induce apoptosis in cancer cells and reduces metastasis via EMT inhibition. Furthermore, Cur supplementation promotes sensitivity to cancer chemotherapy [ 9 ]. However, the health benefits of Cur are limited due to poor bioavailability, so that upon oral administration, a low amount of this valuable compound is absorbed by the intestine and excretion occurs for the rest.…”

Ozonated Olive Oil: Enhanced Cutaneous Delivery via Niosomal Nanovesicles for Melanoma Treatment

“…Furthermore, niosomes can increase the residence time of various drugs in the stratum corneum and epidermis, while minimizing their systemic absorption [ 16 ]. Several studies have reported the encapsulation of different drugs into niosomes, such as topotecan [ 14 ], letrozole [ 17 ], curcumin [ 18 ], and melittin [ 19 ], aiming to improve their hydrophilicity, bioavailability, and anticancer activities.…”