Investigation of the Antitumor Activity and Toxicity of Tumor-Derived Exosomes Fused with Long-Circulating and pH-Sensitive Liposomes Containing Doxorubicin
Exosome–liposome hybrid nanocarriers containing chemotherapeutic agents have been developed to enhance drug delivery, improve the efficacy of the treatment of metastatic cancer, and overcome chemoresistance in cancer therapy. Thus, the objectives of this study were to investigate the toxicological p...
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| Format: | Article |
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MDPI AG
2022-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/11/2256 |
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| author | Eliza Rocha Gomes Fernanda Rezende Souza Geovanni Dantas Cassali Adriano de Paula Sabino André Luis Branco de Barros Mônica Cristina Oliveira |
| author_facet | Eliza Rocha Gomes Fernanda Rezende Souza Geovanni Dantas Cassali Adriano de Paula Sabino André Luis Branco de Barros Mônica Cristina Oliveira |
| author_sort | Eliza Rocha Gomes |
| collection | DOAJ |
| description | Exosome–liposome hybrid nanocarriers containing chemotherapeutic agents have been developed to enhance drug delivery, improve the efficacy of the treatment of metastatic cancer, and overcome chemoresistance in cancer therapy. Thus, the objectives of this study were to investigate the toxicological profiles of exosomes fused with long-circulating and pH-sensitive liposomes containing doxorubicin (ExoSpHL-DOX) in healthy mice and the antitumor activity of ExoSpHL-DOX in Balb/c female mice bearing 4T1 breast tumors. The acute toxicity was determined by evaluating the mortality and morbidity of the animals and conducting hematological, biochemical, and histopathological analyses after a single intravenous administration of ExoSpHL-DOX. The results of the study indicated that the ExoSpHL-DOX treatment is less toxic than the free doxorubicin (DOX) treatment. ExoSpHL-DOX showed no signs of nephrotoxicity, even at the highest dose of DOX, indicating that the hybrid nanosystem may alter the distribution of DOX and reduce the kidney damage. Regarding the antitumor activity, ExoSpHL-DOX showed an antitumor effect compared to the control group. Furthermore, the hybrid nanocarrier of tumor-derived exosomes fused with long-circulating and pH-sensitive liposomes reduced the number of metastatic foci in the lungs. These results indicate that ExoSpHL-DOX may be a promising nanocarrier for the treatment of breast cancer, reducing toxicity and inhibiting metastasis, mainly in the lungs. |
| first_indexed | 2024-03-09T18:45:36Z |
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| id | doaj.art-fa451727bfbb4cd49283a983736c05a5 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T18:45:36Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-fa451727bfbb4cd49283a983736c05a52023-11-24T06:19:10ZengMDPI AGPharmaceutics1999-49232022-10-011411225610.3390/pharmaceutics14112256Investigation of the Antitumor Activity and Toxicity of Tumor-Derived Exosomes Fused with Long-Circulating and pH-Sensitive Liposomes Containing DoxorubicinEliza Rocha Gomes0Fernanda Rezende Souza1Geovanni Dantas Cassali2Adriano de Paula Sabino3André Luis Branco de Barros4Mônica Cristina Oliveira5Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte 31270-901, Minas Gerais, BrazilDepartment of General Pathology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte 31270-901, Minas Gerais, BrazilDepartment of General Pathology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte 31270-901, Minas Gerais, BrazilDepartment of Clinical and Toxicological Analysis, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte 31270-901, Minas Gerais, BrazilDepartment of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte 31270-901, Minas Gerais, BrazilDepartment of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Belo Horizonte 31270-901, Minas Gerais, BrazilExosome–liposome hybrid nanocarriers containing chemotherapeutic agents have been developed to enhance drug delivery, improve the efficacy of the treatment of metastatic cancer, and overcome chemoresistance in cancer therapy. Thus, the objectives of this study were to investigate the toxicological profiles of exosomes fused with long-circulating and pH-sensitive liposomes containing doxorubicin (ExoSpHL-DOX) in healthy mice and the antitumor activity of ExoSpHL-DOX in Balb/c female mice bearing 4T1 breast tumors. The acute toxicity was determined by evaluating the mortality and morbidity of the animals and conducting hematological, biochemical, and histopathological analyses after a single intravenous administration of ExoSpHL-DOX. The results of the study indicated that the ExoSpHL-DOX treatment is less toxic than the free doxorubicin (DOX) treatment. ExoSpHL-DOX showed no signs of nephrotoxicity, even at the highest dose of DOX, indicating that the hybrid nanosystem may alter the distribution of DOX and reduce the kidney damage. Regarding the antitumor activity, ExoSpHL-DOX showed an antitumor effect compared to the control group. Furthermore, the hybrid nanocarrier of tumor-derived exosomes fused with long-circulating and pH-sensitive liposomes reduced the number of metastatic foci in the lungs. These results indicate that ExoSpHL-DOX may be a promising nanocarrier for the treatment of breast cancer, reducing toxicity and inhibiting metastasis, mainly in the lungs.https://www.mdpi.com/1999-4923/14/11/2256acute toxicitybreast cancermetastasisexosomesliposomesdoxorubicin |
| spellingShingle | Eliza Rocha Gomes Fernanda Rezende Souza Geovanni Dantas Cassali Adriano de Paula Sabino André Luis Branco de Barros Mônica Cristina Oliveira Investigation of the Antitumor Activity and Toxicity of Tumor-Derived Exosomes Fused with Long-Circulating and pH-Sensitive Liposomes Containing Doxorubicin Pharmaceutics acute toxicity breast cancer metastasis exosomes liposomes doxorubicin |
| title | Investigation of the Antitumor Activity and Toxicity of Tumor-Derived Exosomes Fused with Long-Circulating and pH-Sensitive Liposomes Containing Doxorubicin |
| title_full | Investigation of the Antitumor Activity and Toxicity of Tumor-Derived Exosomes Fused with Long-Circulating and pH-Sensitive Liposomes Containing Doxorubicin |
| title_fullStr | Investigation of the Antitumor Activity and Toxicity of Tumor-Derived Exosomes Fused with Long-Circulating and pH-Sensitive Liposomes Containing Doxorubicin |
| title_full_unstemmed | Investigation of the Antitumor Activity and Toxicity of Tumor-Derived Exosomes Fused with Long-Circulating and pH-Sensitive Liposomes Containing Doxorubicin |
| title_short | Investigation of the Antitumor Activity and Toxicity of Tumor-Derived Exosomes Fused with Long-Circulating and pH-Sensitive Liposomes Containing Doxorubicin |
| title_sort | investigation of the antitumor activity and toxicity of tumor derived exosomes fused with long circulating and ph sensitive liposomes containing doxorubicin |
| topic | acute toxicity breast cancer metastasis exosomes liposomes doxorubicin |
| url | https://www.mdpi.com/1999-4923/14/11/2256 |
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