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Hybrid Nanosystem Formed by DOX-Loaded Liposomes and Extracellular Vesicles from MDA-MB-231 Is Effective against
Luiza Marques Paschoal Barbosa1, Eliza Rocha Gomes1,2, André Luis Branco de Barros1,3
1Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte 31270-901, MG, Brazil.
Abstract:
Drug delivery selectivity is a challenge for cancer treatment. A hybrid pegylated pH-sensitive liposome-extracellular vesicle isolated from human breast cancer cell MDA-MB-231 was developed to investigate its in vitro activity against breast cancer cells of different molecular profiles to overcome this inconvenience. The hybrid nanosystem was produced by film hydration, and doxorubicin (DOX) was encapsulated in this system using the ammonium sulfate gradient method. The characterization of this hybrid nanosystem revealed a mean diameter of 140.20 ± 2.70 nm, a polydispersity index of 0.102 ± 0.033, an encapsulation efficiency of doxorubicin of 88.9% ± 2.4, and a great storage stability for 90 days at 4 °C. The fusion of extracellular vesicles with liposomes was confirmed by nanoflow cytometry using PE-conjugated human anti-CD63. This hybrid nanosystem demonstrated cytotoxicity against human breast cancer cell lines with different molecular subtypes, enhanced anti-migration properties, and exhibited similar cellular uptake to the free DOX treatment. Preliminary acute toxicity assessments using Balb/C female mice indicated a median lethal dose of 15-17.5 mg/kg, with no evidence of splenic, liver, heart, bone marrow, and renal damage at a dose of 15 mg/kg. These findings suggest the hybrid formulation as a versatile nanocarrier for the treatment of various breast cancer subtypes.
Insights
A novel hybrid nanocarrier combines liposomes and extracellular vesicles for targeted breast cancer treatment. This system effectively delivers doxorubicin, showing potent anti-cancer activity and good stability with minimal toxicity in preliminary studies.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Drug delivery selectivity remains a significant challenge in effective cancer therapy.
- Developing targeted nanocarriers is crucial for improving treatment outcomes in diverse breast cancer subtypes.
Purpose of the Study:
- To develop and characterize a hybrid pegylated pH-sensitive liposome-extracellular vesicle nanocarrier.
- To evaluate the in vitro activity of doxorubicin-loaded hybrid nanocarriers against breast cancer cells with different molecular profiles.
Main Methods:
- Hybrid nanosystem fabrication using film hydration and doxorubicin encapsulation via ammonium sulfate gradient.
- Characterization including particle size, polydispersity index, encapsulation efficiency, and storage stability.
- In vitro cytotoxicity and cellular uptake assays, and in vivo acute toxicity assessment in Balb/C mice.
Main Results:
- The hybrid nanosystem exhibited a mean diameter of 140.20 nm, PDI of 0.102, and 88.9% doxorubicin encapsulation efficiency.
- Demonstrated significant cytotoxicity and anti-migration effects against various breast cancer cell lines.
- Preliminary in vivo studies showed a median lethal dose of 15-17.5 mg/kg with no organ damage at 15 mg/kg.
Conclusions:
- The developed hybrid liposome-extracellular vesicle nanocarrier is a promising platform for targeted doxorubicin delivery.
- This versatile nanocarrier shows potential for treating diverse subtypes of breast cancer with enhanced efficacy and safety.
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