Development of doped ZnO-based biomimicking and tumor-targeted nanotheranostics to improve pancreatic cancer treatment
Abstract Despite different nanomaterials were developed so far against cancer, their potential drawbacks are still scarcely considered. The off-target delivery of a therapeutic compound, as well as the non-specific uptake of these nanomaterials by healthy tissues or organs, and their potential immun...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | Cancer Nanotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12645-022-00140-z |
| _version_ | 1828310021635571712 |
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| author | Sugata Barui Nicolò Maria Percivalle Marzia Conte Bianca Dumontel Luisa Racca Marco Carofiglio Valentina Cauda |
| author_facet | Sugata Barui Nicolò Maria Percivalle Marzia Conte Bianca Dumontel Luisa Racca Marco Carofiglio Valentina Cauda |
| author_sort | Sugata Barui |
| collection | DOAJ |
| description | Abstract Despite different nanomaterials were developed so far against cancer, their potential drawbacks are still scarcely considered. The off-target delivery of a therapeutic compound, as well as the non-specific uptake of these nanomaterials by healthy tissues or organs, and their potential immunogenicity are some of the major issues that still have to be faced prior to a successful clinical translation. This work aims to develop an innovative theranostic, biocompatible, and drug-loaded nanoconstruct based on Gadolinium-doped Zinc Oxide (ZnO-Gd) nanocrystals (NCs), focusing on one of the most lethal diseases, i.e., pancreatic cancer. The use of zinc oxide is motivated by the huge potential of this nanomaterial already demonstrated for in vitro and in vivo applications, while the Gadolinium doping confers magnetic properties useful for diagnostics. Furthermore, an innovative biomimetic shell is here used to coat the NCs: it is composed of a lipid bilayer made from extracellular vesicles (EVs) combined with other synthetic lipids and a peptide targeting the pancreatic tumor microenvironment. To complete the nanoconstruct therapeutic function, Gemcitabine, a first-line drug for pancreatic cancer treatment, was adsorbed on the ZnO-Gd NCs prior to the coating with the above-mentioned lipidic shell. The aim of this work is thus to strongly enhance the therapeutic capability of the final nanoconstruct, providing it with high biocompatibility, colloidal stability in biological media, efficient cargo loading and release properties, as well as active targeting for site-selective drug delivery. Furthermore, the magnetic properties of the ZnO-Gd NCs core can in future allow efficient in situ bioimaging capabilities based on Magnetic Resonance Imaging technique. The obtained nanoconstructs were tested on two different pancreatic cancer cell lines, i.e., BxPC-3 and the metastatic AsPC-1, proving high cell internalization levels, mediated by the targeting peptide exposed on the nanoconstruct. Cellular cytotoxicity assay performed on both cell lines dictated ~ 20% increased cell killing efficacy of Gemcitabine when delivered through the nanoconstruct rather than as a free drug. Taken together, our designed theranostic nanoconstruct can have a significant impact on the standard treatment of pancreatic cancer. |
| first_indexed | 2024-04-13T15:37:55Z |
| format | Article |
| id | doaj.art-b286b4566ffb4b2ea74726dfccc9c483 |
| institution | Directory Open Access Journal |
| issn | 1868-6958 1868-6966 |
| language | English |
| last_indexed | 2024-04-13T15:37:55Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Nanotechnology |
| spelling | doaj.art-b286b4566ffb4b2ea74726dfccc9c4832022-12-22T02:41:14ZengBMCCancer Nanotechnology1868-69581868-69662022-11-0113112410.1186/s12645-022-00140-zDevelopment of doped ZnO-based biomimicking and tumor-targeted nanotheranostics to improve pancreatic cancer treatmentSugata Barui0Nicolò Maria Percivalle1Marzia Conte2Bianca Dumontel3Luisa Racca4Marco Carofiglio5Valentina Cauda6Department of Applied Science and Technology, Politecnico di TorinoDepartment of Applied Science and Technology, Politecnico di TorinoDepartment of Applied Science and Technology, Politecnico di TorinoDepartment of Applied Science and Technology, Politecnico di TorinoDepartment of Applied Science and Technology, Politecnico di TorinoDepartment of Applied Science and Technology, Politecnico di TorinoDepartment of Applied Science and Technology, Politecnico di TorinoAbstract Despite different nanomaterials were developed so far against cancer, their potential drawbacks are still scarcely considered. The off-target delivery of a therapeutic compound, as well as the non-specific uptake of these nanomaterials by healthy tissues or organs, and their potential immunogenicity are some of the major issues that still have to be faced prior to a successful clinical translation. This work aims to develop an innovative theranostic, biocompatible, and drug-loaded nanoconstruct based on Gadolinium-doped Zinc Oxide (ZnO-Gd) nanocrystals (NCs), focusing on one of the most lethal diseases, i.e., pancreatic cancer. The use of zinc oxide is motivated by the huge potential of this nanomaterial already demonstrated for in vitro and in vivo applications, while the Gadolinium doping confers magnetic properties useful for diagnostics. Furthermore, an innovative biomimetic shell is here used to coat the NCs: it is composed of a lipid bilayer made from extracellular vesicles (EVs) combined with other synthetic lipids and a peptide targeting the pancreatic tumor microenvironment. To complete the nanoconstruct therapeutic function, Gemcitabine, a first-line drug for pancreatic cancer treatment, was adsorbed on the ZnO-Gd NCs prior to the coating with the above-mentioned lipidic shell. The aim of this work is thus to strongly enhance the therapeutic capability of the final nanoconstruct, providing it with high biocompatibility, colloidal stability in biological media, efficient cargo loading and release properties, as well as active targeting for site-selective drug delivery. Furthermore, the magnetic properties of the ZnO-Gd NCs core can in future allow efficient in situ bioimaging capabilities based on Magnetic Resonance Imaging technique. The obtained nanoconstructs were tested on two different pancreatic cancer cell lines, i.e., BxPC-3 and the metastatic AsPC-1, proving high cell internalization levels, mediated by the targeting peptide exposed on the nanoconstruct. Cellular cytotoxicity assay performed on both cell lines dictated ~ 20% increased cell killing efficacy of Gemcitabine when delivered through the nanoconstruct rather than as a free drug. Taken together, our designed theranostic nanoconstruct can have a significant impact on the standard treatment of pancreatic cancer.https://doi.org/10.1186/s12645-022-00140-zDoped zinc oxide nanocrystalsExtracellular vesiclesTargeted nanotheranosticsPancreatic cancerMagnetic resonance imagingGemcitabine |
| spellingShingle | Sugata Barui Nicolò Maria Percivalle Marzia Conte Bianca Dumontel Luisa Racca Marco Carofiglio Valentina Cauda Development of doped ZnO-based biomimicking and tumor-targeted nanotheranostics to improve pancreatic cancer treatment Cancer Nanotechnology Doped zinc oxide nanocrystals Extracellular vesicles Targeted nanotheranostics Pancreatic cancer Magnetic resonance imaging Gemcitabine |
| title | Development of doped ZnO-based biomimicking and tumor-targeted nanotheranostics to improve pancreatic cancer treatment |
| title_full | Development of doped ZnO-based biomimicking and tumor-targeted nanotheranostics to improve pancreatic cancer treatment |
| title_fullStr | Development of doped ZnO-based biomimicking and tumor-targeted nanotheranostics to improve pancreatic cancer treatment |
| title_full_unstemmed | Development of doped ZnO-based biomimicking and tumor-targeted nanotheranostics to improve pancreatic cancer treatment |
| title_short | Development of doped ZnO-based biomimicking and tumor-targeted nanotheranostics to improve pancreatic cancer treatment |
| title_sort | development of doped zno based biomimicking and tumor targeted nanotheranostics to improve pancreatic cancer treatment |
| topic | Doped zinc oxide nanocrystals Extracellular vesicles Targeted nanotheranostics Pancreatic cancer Magnetic resonance imaging Gemcitabine |
| url | https://doi.org/10.1186/s12645-022-00140-z |
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