Folate-Targeted PEGylated Magnetoliposomes for Hyperthermia-Mediated Controlled Release of Doxorubicin
Doxorubicin (DOX) is a chemotherapeutic agent commonly used for the treatment of solid tumors. However, the cardiotoxicity associated with its prolonged use prevents further adherence and therapeutic efficacy. By encapsulating DOX within a PEGylated liposome, Doxil® considerably decreased DOX cardio...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.854430/full |
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| author | Emílio R. Cintra Tacio G. Hayasaki Ailton A. Sousa-Junior Artur C. G. Silva Marize C. Valadares Andris F. Bakuzis Andris F. Bakuzis Sebastião A. Mendanha Sebastião A. Mendanha Sebastião A. Mendanha Eliana M. Lima Eliana M. Lima |
| author_facet | Emílio R. Cintra Tacio G. Hayasaki Ailton A. Sousa-Junior Artur C. G. Silva Marize C. Valadares Andris F. Bakuzis Andris F. Bakuzis Sebastião A. Mendanha Sebastião A. Mendanha Sebastião A. Mendanha Eliana M. Lima Eliana M. Lima |
| author_sort | Emílio R. Cintra |
| collection | DOAJ |
| description | Doxorubicin (DOX) is a chemotherapeutic agent commonly used for the treatment of solid tumors. However, the cardiotoxicity associated with its prolonged use prevents further adherence and therapeutic efficacy. By encapsulating DOX within a PEGylated liposome, Doxil® considerably decreased DOX cardiotoxicity. By using thermally sensitive lysolipids in its bilayer composition, ThermoDox® implemented a heat-induced controlled release of DOX. However, both ThermoDox® and Doxil® rely on their passive retention in tumors, depending on their half-lives in blood. Moreover, ThermoDox® ordinarily depend on invasive radiofrequency-generating metallic probes for local heating. In this study, we prepare, characterize, and evaluate the antitumoral capabilities of DOX-loaded folate-targeted PEGylated magnetoliposomes (DFPML). Unlike ThermoDox®, DOX delivery via DFPML is mediated by the heat released through dynamic hysteresis losses from magnetothermal converting systems composed by MnFe2O4 nanoparticles (NPs) under AC magnetic field excitation—a non-invasive technique designated magnetic hyperthermia (MHT). Moreover, DFPML dismisses the use of thermally sensitive lysolipids, allowing the use of simpler and cheaper alternative lipids. MnFe2O4 NPs and DFPML are fully characterized in terms of their size, morphology, polydispersion, magnetic, and magnetothermal properties. About 50% of the DOX load is released from DFPML after 30 min under MHT conditions. Being folate-targeted, in vitro DFPML antitumoral activity is higher (IC50 ≈ 1 μg/ml) for folate receptor-overexpressing B16F10 murine melanoma cells, compared to MCF7 human breast adenocarcinoma cells (IC50 ≈ 4 μg/ml). Taken together, our results indicate that DFPML are strong candidates for folate-targeted anticancer therapies based on DOX controlled release. |
| first_indexed | 2024-12-13T09:36:41Z |
| format | Article |
| id | doaj.art-e86d0dc5db704862abf7457ade439700 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T09:36:41Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-e86d0dc5db704862abf7457ade4397002022-12-21T23:52:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-03-011310.3389/fphar.2022.854430854430Folate-Targeted PEGylated Magnetoliposomes for Hyperthermia-Mediated Controlled Release of DoxorubicinEmílio R. Cintra0Tacio G. Hayasaki1Ailton A. Sousa-Junior2Artur C. G. Silva3Marize C. Valadares4Andris F. Bakuzis5Andris F. Bakuzis6Sebastião A. Mendanha7Sebastião A. Mendanha8Sebastião A. Mendanha9Eliana M. Lima10Eliana M. Lima11FarmaTec—Laboratory of Pharmaceutical Technology, School of Pharmacy, Federal University of Goias, Goiania, BrazilFarmaTec—Laboratory of Pharmaceutical Technology, School of Pharmacy, Federal University of Goias, Goiania, BrazilFarmaTec—Laboratory of Pharmaceutical Technology, School of Pharmacy, Federal University of Goias, Goiania, BrazilToxin—Laboratory of Education and Research in In Vitro Toxicology, School of Pharmacy, Federal University of Goias, Goiania, BrazilToxin—Laboratory of Education and Research in In Vitro Toxicology, School of Pharmacy, Federal University of Goias, Goiania, BrazilPhysics Institute, Federal University of Goias, Goiania, BrazilCNanoMed—Nanomedicine Integrated Research Center, Federal University of Goias, Goiania, BrazilFarmaTec—Laboratory of Pharmaceutical Technology, School of Pharmacy, Federal University of Goias, Goiania, BrazilPhysics Institute, Federal University of Goias, Goiania, BrazilCNanoMed—Nanomedicine Integrated Research Center, Federal University of Goias, Goiania, BrazilFarmaTec—Laboratory of Pharmaceutical Technology, School of Pharmacy, Federal University of Goias, Goiania, BrazilCNanoMed—Nanomedicine Integrated Research Center, Federal University of Goias, Goiania, BrazilDoxorubicin (DOX) is a chemotherapeutic agent commonly used for the treatment of solid tumors. However, the cardiotoxicity associated with its prolonged use prevents further adherence and therapeutic efficacy. By encapsulating DOX within a PEGylated liposome, Doxil® considerably decreased DOX cardiotoxicity. By using thermally sensitive lysolipids in its bilayer composition, ThermoDox® implemented a heat-induced controlled release of DOX. However, both ThermoDox® and Doxil® rely on their passive retention in tumors, depending on their half-lives in blood. Moreover, ThermoDox® ordinarily depend on invasive radiofrequency-generating metallic probes for local heating. In this study, we prepare, characterize, and evaluate the antitumoral capabilities of DOX-loaded folate-targeted PEGylated magnetoliposomes (DFPML). Unlike ThermoDox®, DOX delivery via DFPML is mediated by the heat released through dynamic hysteresis losses from magnetothermal converting systems composed by MnFe2O4 nanoparticles (NPs) under AC magnetic field excitation—a non-invasive technique designated magnetic hyperthermia (MHT). Moreover, DFPML dismisses the use of thermally sensitive lysolipids, allowing the use of simpler and cheaper alternative lipids. MnFe2O4 NPs and DFPML are fully characterized in terms of their size, morphology, polydispersion, magnetic, and magnetothermal properties. About 50% of the DOX load is released from DFPML after 30 min under MHT conditions. Being folate-targeted, in vitro DFPML antitumoral activity is higher (IC50 ≈ 1 μg/ml) for folate receptor-overexpressing B16F10 murine melanoma cells, compared to MCF7 human breast adenocarcinoma cells (IC50 ≈ 4 μg/ml). Taken together, our results indicate that DFPML are strong candidates for folate-targeted anticancer therapies based on DOX controlled release.https://www.frontiersin.org/articles/10.3389/fphar.2022.854430/fullmagnetoliposomesdoxorubicinmagnetic hyperthermiafolic acidB16F10MCF7 |
| spellingShingle | Emílio R. Cintra Tacio G. Hayasaki Ailton A. Sousa-Junior Artur C. G. Silva Marize C. Valadares Andris F. Bakuzis Andris F. Bakuzis Sebastião A. Mendanha Sebastião A. Mendanha Sebastião A. Mendanha Eliana M. Lima Eliana M. Lima Folate-Targeted PEGylated Magnetoliposomes for Hyperthermia-Mediated Controlled Release of Doxorubicin Frontiers in Pharmacology magnetoliposomes doxorubicin magnetic hyperthermia folic acid B16F10 MCF7 |
| title | Folate-Targeted PEGylated Magnetoliposomes for Hyperthermia-Mediated Controlled Release of Doxorubicin |
| title_full | Folate-Targeted PEGylated Magnetoliposomes for Hyperthermia-Mediated Controlled Release of Doxorubicin |
| title_fullStr | Folate-Targeted PEGylated Magnetoliposomes for Hyperthermia-Mediated Controlled Release of Doxorubicin |
| title_full_unstemmed | Folate-Targeted PEGylated Magnetoliposomes for Hyperthermia-Mediated Controlled Release of Doxorubicin |
| title_short | Folate-Targeted PEGylated Magnetoliposomes for Hyperthermia-Mediated Controlled Release of Doxorubicin |
| title_sort | folate targeted pegylated magnetoliposomes for hyperthermia mediated controlled release of doxorubicin |
| topic | magnetoliposomes doxorubicin magnetic hyperthermia folic acid B16F10 MCF7 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.854430/full |
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