cRGD-Functionalized Silk Fibroin Nanoparticles: A Strategy for Cancer Treatment with a Potent Unselective Naphthalene Diimide Derivative
Developing drug delivery systems to target cytotoxic drugs directly into tumor cells is still a compelling need with regard to reducing side effects and improving the efficacy of cancer chemotherapy. In this work, silk fibroin nanoparticles (SFNs) have been designed to load a previously described cy...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/6/1725 |
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| author | Valentina Pirota Giovanni Bisbano Massimo Serra Maria Luisa Torre Filippo Doria Elia Bari Mayra Paolillo |
| author_facet | Valentina Pirota Giovanni Bisbano Massimo Serra Maria Luisa Torre Filippo Doria Elia Bari Mayra Paolillo |
| author_sort | Valentina Pirota |
| collection | DOAJ |
| description | Developing drug delivery systems to target cytotoxic drugs directly into tumor cells is still a compelling need with regard to reducing side effects and improving the efficacy of cancer chemotherapy. In this work, silk fibroin nanoparticles (SFNs) have been designed to load a previously described cytotoxic compound (NDI-1) that disrupts the cell cycle by specifically interacting with non-canonical secondary structures of DNA. SFNs were then functionalized on their surface with cyclic pentapeptides incorporating the Arg-Gly-Asp sequence (<i>c</i>RGDs) to provide active targeting toward glioma cell lines that abundantly express ανβ3 and ανβ5 integrin receptors. Cytotoxicity and selective targeting were assessed by in vitro tests on human glioma cell lines U373 (highly-expressing integrin subunits) and D384 cell lines (low-expressing integrin subunits in comparison to U373). SFNs were of nanometric size (d<sub>50</sub> less than 100 nm), round shaped with a smooth surface, and with a negative surface charge; overall, these characteristics made them very likely to be taken up by cells. The active NDI-1 was loaded into SFNs with high encapsulation efficiency and was not released before the internalization and degradation by cells. Functionalization with <i>c</i>RGDs provided selectivity in cell uptake and thus cytotoxicity, with a significantly higher cytotoxic effect of NDI-1 delivered by cRGD-SFNs on U373 cells than on D384 cells. This manuscript provides an in vitro proof-of-concept of <i>c</i>RGD-silk fibroin nanoparticles’ active site-specific targeting of tumors, paving the way for further in vivo efficacy tests. |
| first_indexed | 2024-03-11T06:48:27Z |
| format | Article |
| id | doaj.art-378304c267a54adb808ec8dfe5ac7816 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T06:48:27Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-378304c267a54adb808ec8dfe5ac78162023-11-17T10:06:20ZengMDPI AGCancers2072-66942023-03-01156172510.3390/cancers15061725cRGD-Functionalized Silk Fibroin Nanoparticles: A Strategy for Cancer Treatment with a Potent Unselective Naphthalene Diimide DerivativeValentina Pirota0Giovanni Bisbano1Massimo Serra2Maria Luisa Torre3Filippo Doria4Elia Bari5Mayra Paolillo6Department of Chemistry, University of Pavia, Viale Taramelli 10, 27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, ItalyDepartment of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, ItalyDepartment of Pharmaceutical Sciences, University of Piemonte Orientale, Largo Donegani 2/3, 28100 Novara, ItalyDepartment of Chemistry, University of Pavia, Viale Taramelli 10, 27100 Pavia, ItalyDepartment of Pharmaceutical Sciences, University of Piemonte Orientale, Largo Donegani 2/3, 28100 Novara, ItalyDepartment of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, ItalyDeveloping drug delivery systems to target cytotoxic drugs directly into tumor cells is still a compelling need with regard to reducing side effects and improving the efficacy of cancer chemotherapy. In this work, silk fibroin nanoparticles (SFNs) have been designed to load a previously described cytotoxic compound (NDI-1) that disrupts the cell cycle by specifically interacting with non-canonical secondary structures of DNA. SFNs were then functionalized on their surface with cyclic pentapeptides incorporating the Arg-Gly-Asp sequence (<i>c</i>RGDs) to provide active targeting toward glioma cell lines that abundantly express ανβ3 and ανβ5 integrin receptors. Cytotoxicity and selective targeting were assessed by in vitro tests on human glioma cell lines U373 (highly-expressing integrin subunits) and D384 cell lines (low-expressing integrin subunits in comparison to U373). SFNs were of nanometric size (d<sub>50</sub> less than 100 nm), round shaped with a smooth surface, and with a negative surface charge; overall, these characteristics made them very likely to be taken up by cells. The active NDI-1 was loaded into SFNs with high encapsulation efficiency and was not released before the internalization and degradation by cells. Functionalization with <i>c</i>RGDs provided selectivity in cell uptake and thus cytotoxicity, with a significantly higher cytotoxic effect of NDI-1 delivered by cRGD-SFNs on U373 cells than on D384 cells. This manuscript provides an in vitro proof-of-concept of <i>c</i>RGD-silk fibroin nanoparticles’ active site-specific targeting of tumors, paving the way for further in vivo efficacy tests.https://www.mdpi.com/2072-6694/15/6/1725RGDsilk fibroin nanoparticlesintegrin antagonistnaphthalene diimidesanticanceractive targeting |
| spellingShingle | Valentina Pirota Giovanni Bisbano Massimo Serra Maria Luisa Torre Filippo Doria Elia Bari Mayra Paolillo cRGD-Functionalized Silk Fibroin Nanoparticles: A Strategy for Cancer Treatment with a Potent Unselective Naphthalene Diimide Derivative Cancers RGD silk fibroin nanoparticles integrin antagonist naphthalene diimides anticancer active targeting |
| title | cRGD-Functionalized Silk Fibroin Nanoparticles: A Strategy for Cancer Treatment with a Potent Unselective Naphthalene Diimide Derivative |
| title_full | cRGD-Functionalized Silk Fibroin Nanoparticles: A Strategy for Cancer Treatment with a Potent Unselective Naphthalene Diimide Derivative |
| title_fullStr | cRGD-Functionalized Silk Fibroin Nanoparticles: A Strategy for Cancer Treatment with a Potent Unselective Naphthalene Diimide Derivative |
| title_full_unstemmed | cRGD-Functionalized Silk Fibroin Nanoparticles: A Strategy for Cancer Treatment with a Potent Unselective Naphthalene Diimide Derivative |
| title_short | cRGD-Functionalized Silk Fibroin Nanoparticles: A Strategy for Cancer Treatment with a Potent Unselective Naphthalene Diimide Derivative |
| title_sort | crgd functionalized silk fibroin nanoparticles a strategy for cancer treatment with a potent unselective naphthalene diimide derivative |
| topic | RGD silk fibroin nanoparticles integrin antagonist naphthalene diimides anticancer active targeting |
| url | https://www.mdpi.com/2072-6694/15/6/1725 |
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