Nose-to-brain selective drug delivery to glioma via ferritin-based nanovectors reduces tumor growth and improves survival rate
Abstract Gliomas are among the most fatal tumors, and the available therapeutic options are very limited. Additionally, the blood-brain barrier (BBB) prevents most drugs from entering the brain. We designed and produced a ferritin-based stimuli-sensitive nanocarrier with high biocompatibility and wa...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2024-04-01
|
| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-024-06653-2 |
| _version_ | 1797208998172164096 |
|---|---|
| author | Francesco Marrocco Elisabetta Falvo Luciana Mosca Giada Tisci Alessandro Arcovito Alice Reccagni Cristina Limatola Roberta Bernardini Pierpaolo Ceci Giuseppina D’Alessandro Gianni Colotti |
| author_facet | Francesco Marrocco Elisabetta Falvo Luciana Mosca Giada Tisci Alessandro Arcovito Alice Reccagni Cristina Limatola Roberta Bernardini Pierpaolo Ceci Giuseppina D’Alessandro Gianni Colotti |
| author_sort | Francesco Marrocco |
| collection | DOAJ |
| description | Abstract Gliomas are among the most fatal tumors, and the available therapeutic options are very limited. Additionally, the blood-brain barrier (BBB) prevents most drugs from entering the brain. We designed and produced a ferritin-based stimuli-sensitive nanocarrier with high biocompatibility and water solubility. It can incorporate high amounts of the potent topoisomerase 1 inhibitor Genz-644282. Here, we show that this nanocarrier, named The-0504, can cross the BBB and specifically deliver the payload to gliomas that express high amounts of the ferritin/transferrin receptor TfR1 (CD71). Intranasal or intravenous administration of The-0504 both reduce tumor growth and improve the survival rate of glioma-bearing mice. However, nose-to-brain administration is a simpler and less invasive route that may spare most of the healthy tissues compared to intravenous injections. For this reason, the data reported here could pave the way towards a new, safe, and direct ferritin-based drug delivery method for brain diseases, especially brain tumors. |
| first_indexed | 2024-04-24T09:47:42Z |
| format | Article |
| id | doaj.art-6e3bf7316b2d4140a4a9dc60640a5167 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-04-24T09:47:42Z |
| publishDate | 2024-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-6e3bf7316b2d4140a4a9dc60640a51672024-04-14T11:30:46ZengNature Publishing GroupCell Death and Disease2041-48892024-04-0115411010.1038/s41419-024-06653-2Nose-to-brain selective drug delivery to glioma via ferritin-based nanovectors reduces tumor growth and improves survival rateFrancesco Marrocco0Elisabetta Falvo1Luciana Mosca2Giada Tisci3Alessandro Arcovito4Alice Reccagni5Cristina Limatola6Roberta Bernardini7Pierpaolo Ceci8Giuseppina D’Alessandro9Gianni Colotti10Department of Physiology and Pharmacology, Sapienza UniversityInstitute of Molecular Biology and Pathology, Italian National Research Council IBPM-CNRDepartment of Biochemical Sciences, Sapienza UniversityDepartment of Biochemical Sciences, Sapienza UniversityDipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro CuoreDepartment of Physiology and Pharmacology, Sapienza UniversityDepartment of Physiology and Pharmacology, Sapienza University, Laboratory affiliated to Institute 17 Pasteur ItaliaDipartimento di Scienze Cliniche e Medicina Traslazionale Università degli Studi di Roma “Tor Vergata”Institute of Molecular Biology and Pathology, Italian National Research Council IBPM-CNRDepartment of Physiology and Pharmacology, Sapienza UniversityInstitute of Molecular Biology and Pathology, Italian National Research Council IBPM-CNRAbstract Gliomas are among the most fatal tumors, and the available therapeutic options are very limited. Additionally, the blood-brain barrier (BBB) prevents most drugs from entering the brain. We designed and produced a ferritin-based stimuli-sensitive nanocarrier with high biocompatibility and water solubility. It can incorporate high amounts of the potent topoisomerase 1 inhibitor Genz-644282. Here, we show that this nanocarrier, named The-0504, can cross the BBB and specifically deliver the payload to gliomas that express high amounts of the ferritin/transferrin receptor TfR1 (CD71). Intranasal or intravenous administration of The-0504 both reduce tumor growth and improve the survival rate of glioma-bearing mice. However, nose-to-brain administration is a simpler and less invasive route that may spare most of the healthy tissues compared to intravenous injections. For this reason, the data reported here could pave the way towards a new, safe, and direct ferritin-based drug delivery method for brain diseases, especially brain tumors.https://doi.org/10.1038/s41419-024-06653-2 |
| spellingShingle | Francesco Marrocco Elisabetta Falvo Luciana Mosca Giada Tisci Alessandro Arcovito Alice Reccagni Cristina Limatola Roberta Bernardini Pierpaolo Ceci Giuseppina D’Alessandro Gianni Colotti Nose-to-brain selective drug delivery to glioma via ferritin-based nanovectors reduces tumor growth and improves survival rate Cell Death and Disease |
| title | Nose-to-brain selective drug delivery to glioma via ferritin-based nanovectors reduces tumor growth and improves survival rate |
| title_full | Nose-to-brain selective drug delivery to glioma via ferritin-based nanovectors reduces tumor growth and improves survival rate |
| title_fullStr | Nose-to-brain selective drug delivery to glioma via ferritin-based nanovectors reduces tumor growth and improves survival rate |
| title_full_unstemmed | Nose-to-brain selective drug delivery to glioma via ferritin-based nanovectors reduces tumor growth and improves survival rate |
| title_short | Nose-to-brain selective drug delivery to glioma via ferritin-based nanovectors reduces tumor growth and improves survival rate |
| title_sort | nose to brain selective drug delivery to glioma via ferritin based nanovectors reduces tumor growth and improves survival rate |
| url | https://doi.org/10.1038/s41419-024-06653-2 |
| work_keys_str_mv | AT francescomarrocco nosetobrainselectivedrugdeliverytogliomaviaferritinbasednanovectorsreducestumorgrowthandimprovessurvivalrate AT elisabettafalvo nosetobrainselectivedrugdeliverytogliomaviaferritinbasednanovectorsreducestumorgrowthandimprovessurvivalrate AT lucianamosca nosetobrainselectivedrugdeliverytogliomaviaferritinbasednanovectorsreducestumorgrowthandimprovessurvivalrate AT giadatisci nosetobrainselectivedrugdeliverytogliomaviaferritinbasednanovectorsreducestumorgrowthandimprovessurvivalrate AT alessandroarcovito nosetobrainselectivedrugdeliverytogliomaviaferritinbasednanovectorsreducestumorgrowthandimprovessurvivalrate AT alicereccagni nosetobrainselectivedrugdeliverytogliomaviaferritinbasednanovectorsreducestumorgrowthandimprovessurvivalrate AT cristinalimatola nosetobrainselectivedrugdeliverytogliomaviaferritinbasednanovectorsreducestumorgrowthandimprovessurvivalrate AT robertabernardini nosetobrainselectivedrugdeliverytogliomaviaferritinbasednanovectorsreducestumorgrowthandimprovessurvivalrate AT pierpaoloceci nosetobrainselectivedrugdeliverytogliomaviaferritinbasednanovectorsreducestumorgrowthandimprovessurvivalrate AT giuseppinadalessandro nosetobrainselectivedrugdeliverytogliomaviaferritinbasednanovectorsreducestumorgrowthandimprovessurvivalrate AT giannicolotti nosetobrainselectivedrugdeliverytogliomaviaferritinbasednanovectorsreducestumorgrowthandimprovessurvivalrate |