Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in vivo evaluation of anti-cancer effect

Dabbagh Moghaddam, F ; Sharif University of Technology | 2021

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  1. Type of Document: Article
  2. DOI: 10.1186/s12645-021-00085-9
  3. Publisher: BioMed Central Ltd , 2021
  4. Abstract:
  5. Background: Melittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, melittin, melittin-loaded niosome, and empty niosome had been optimized and the anticancer effect assessed in vitro on 4T1 and SKBR3 breast cell lines and in vivo on BALB/C inbred mice. "Thin-layer hydration method" was used for preparing the niosomes; different niosomal formulations of melittin were prepared and characterized in terms of morphology, size, polydispersity index, encapsulation efficiency, release kinetics, and stability. A niosome was formulated and loaded with melittin as a promising drug carrier system for chemotherapy of the breast cancer cells. Hemolysis, apoptosis, cell cytotoxicity, invasion and migration of selected concentrations of melittin, and melittin-loaded niosome were evaluated on 4T1 and SKBR3 cells using hemolytic activity assay, flow cytometry, MTT assay, soft agar colony assay, and wound healing assay. Real-time PCR was used to determine the gene expression. 40 BALB/c inbred mice were used; then, the histopathology, P53 immunohistochemical assay and estimate of renal and liver enzyme activity for all groups had been done. Results: This study showed melittin-loaded niosome is an excellent substitute in breast cancer treatment due to enhanced targeting, encapsulation efficiency, PDI, and release rate and shows a high anticancer effect on cell lines. The melittin-loaded niosome affects the genes expression by studied cells were higher than other samples; down-regulates the expression of Bcl2, MMP2, and MMP9 genes while they up-regulate the expression of Bax, Caspase3 and Caspase9 genes. They have also enhanced the apoptosis rate and inhibited cell migration, invasion in both cell lines compared to the melittin samples. Results of histopathology showed reduce mitosis index, invasion and pleomorphism in melittin-loaded niosome. Renal and hepatic biomarker activity did not significantly differ in melittin-loaded niosome and melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups. Conclusions: Our study successfully declares that melittin-loaded niosome had more anti-cancer effects than free melittin. This project has demonstrated that niosomes are suitable vesicle carriers for melittin, compare to the free form. © 2021, The Author(s)
  6. Keywords:
  7. Alanine aminotransferase ; Alkaline phosphatase ; Aspartate aminotransferase ; Biological marker ; Caspase 3 ; Caspase 9 ; Creatinine ; Estrogen receptor ; Gelatinase B ; Liposome ; Liver enzyme ; Melittin ; Nanochain ; Nanoparticle ; Niosome ; Protein Bax ; Protein bcl 2 ; Protein p53 ; 4T1 cell line ; Angiogenesis ; Animal experiment ; Animal model ; Animal tissue ; Antifungal activity ; Antineoplastic activity ; Apoptosis ; Apoptosis rate ; Biocompatibility ; Breast cancer ; Cancer therapy ; Carcinogenesis ; Cell invasion ; Cell migration ; Cell proliferation ; Cell survival ; Cell viability ; Chemotherapy ; Colony formation ; Controlled study ; Cytotoxicity ; Down regulation ; Drug formulation ; Drug release ; Encapsulation ; Enzyme activity ; Flow cytometry ; Gene expression ; Hemolysis ; Histopathology ; Hydration ; IC50 ; Immunohistochemistry ; In vitro study ; In vivo study ; Infrared spectroscopy ; Iron kinetics ; Metastatic breast cancer ; Mitosis index ; Mouse ; MTT assay ; Nonhuman ; Particle size ; Protein expression ; Real time polymerase chain reaction ; RNA extraction ; Scoring system ; SK-BR-3 cell line ; Transmission electron microscopy ; Tumor growth ; Tumor invasion ; Tumor volume ; TUNEL assay ; Upregulation ; Urea nitrogen blood level ; Wound healing ; Wound healing assay ; Zeta potential
  8. Source: Cancer Nanotechnology ; Volume 12, Issue 1 , 2021 ; 18686958 (ISSN)
  9. URL: https://cancer-nano.biomedcentral.com/articles/10.1186/s12645-021-00085-9