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

Hamidreza Sahrayi,Chaiyavat Chaiyasut,Elham Hosseini,Iman Akbarzadeh,Nazanin Khayam,Clare Hoskins,Mohammed Bhia,Sahar Amiri,Mahsa Bourbour,Bahareh Farasati Far,Sara Karimifard,Seyed Mohammadmahdi Meybodi

doi:10.3390/ph15010006

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.

Highlights

Breast cancer is the most common type of cancer in women with millions of new cases detected annually
Niosome nanoparticles containing an equal amount of Let and Cyclo drugs (10 mg each) at varied surfactant: cholesterol (1:1 and 2:1) and lipid: drug (10:1 and 20:1) molar ratios were prepared
The data showed that particle size of niosomes increased with the use of higher lipid-to-drug molar ratios

Summary

Introduction

Breast cancer is the most common type of cancer in women with millions of new cases detected annually. Due to the cancer cell metabolism’s complexity, there is no exact treatment method, but two common local treatments, such as surgery and radiotherapy, and systemic ones, such as chemotherapy and hormone therapy, are widely used [2,3]. The metastasized cells can reform tumors after removal of the primary tumor, causing patient remission. Alternatives, such as radiotherapy [4,5] or chemotherapy, are highly non-specific to the cancerous tissue causing widespread tissue damage and harsh patient side effects. The non-specificity of chemotherapy results in low delivery efficiency towards the site of need requiring high-dose administration to reach the therapeutic window [4] or to overcome drug resistance, resulting in greater and more severe side effects [5]

Methods

Results

Conclusion