Targeting of immunosuppressive myeloid cells from glioblastoma patients by modulation of size and surface charge of lipid nanocapsules
Abstract Background Myeloid derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are two of the major players involved in the inhibition of anti-tumor immune response in cancer patients, leading to poor prognosis. Selective targeting of myeloid cells has therefore become an attra...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-02-01
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| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12951-020-00589-3 |
| _version_ | 1828346367847694336 |
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| author | Laura Pinton Sara Magri Elena Masetto Marina Vettore Ilaria Schibuola Vincenzo Ingangi Ilaria Marigo Kevin Matha Jean-Pierre Benoit Alessandro Della Puppa Vincenzo Bronte Giovanna Lollo Susanna Mandruzzato |
| author_facet | Laura Pinton Sara Magri Elena Masetto Marina Vettore Ilaria Schibuola Vincenzo Ingangi Ilaria Marigo Kevin Matha Jean-Pierre Benoit Alessandro Della Puppa Vincenzo Bronte Giovanna Lollo Susanna Mandruzzato |
| author_sort | Laura Pinton |
| collection | DOAJ |
| description | Abstract Background Myeloid derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are two of the major players involved in the inhibition of anti-tumor immune response in cancer patients, leading to poor prognosis. Selective targeting of myeloid cells has therefore become an attractive therapeutic strategy to relieve immunosuppression and, in this frame, we previously demonstrated that lipid nanocapsules (LNCs) loaded with lauroyl-modified gemcitabine efficiently target monocytic MDSCs in melanoma patients. In this study, we investigated the impact of the physico-chemical characteristics of LNCs, namely size and surface potential, towards immunosuppressive cell targeting. We exploited myeloid cells isolated from glioblastoma patients, which play a relevant role in the immunosuppression, to demonstrate that tailored nanosystems can target not only tumor cells but also tumor-promoting cells, thus constituting an efficient system that could be used to inhibit their function. Results The incorporation of different LNC formulations with a size of 100 nm, carrying overall positive, neutral or negative charge, was evaluated on leukocytes and tumor-infiltrating cells freshly isolated from glioblastoma patients. We observed that the maximum LNC uptake was obtained in monocytes with neutral 100 nm LNCs, while positively charged 100 nm LNCs were more effective on macrophages and tumor cells, maintaining at low level the incorporation by T cells. The mechanism of uptake was elucidated, demonstrating that LNCs are incorporated mainly by caveolae-mediated endocytosis. Conclusions We demonstrated that LNCs can be directed towards immunosuppressive cells by simply modulating their size and charge thus providing a novel approach to exploit nanosystems for anticancer treatment in the frame of immunotherapy. |
| first_indexed | 2024-04-14T00:25:51Z |
| format | Article |
| id | doaj.art-9c645bdba4b44adb9a8597591183c940 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-14T00:25:51Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-9c645bdba4b44adb9a8597591183c9402022-12-22T02:22:45ZengBMCJournal of Nanobiotechnology1477-31552020-02-0118111210.1186/s12951-020-00589-3Targeting of immunosuppressive myeloid cells from glioblastoma patients by modulation of size and surface charge of lipid nanocapsulesLaura Pinton0Sara Magri1Elena Masetto2Marina Vettore3Ilaria Schibuola4Vincenzo Ingangi5Ilaria Marigo6Kevin Matha7Jean-Pierre Benoit8Alessandro Della Puppa9Vincenzo Bronte10Giovanna Lollo11Susanna Mandruzzato12Veneto Institute of Oncology IOV–IRCCSDepartment of Surgery, Oncology and Gastroenterology, University of PadovaVeneto Institute of Oncology IOV–IRCCSVeneto Institute of Oncology IOV–IRCCSDepartment of Surgery, Oncology and Gastroenterology, University of PadovaVeneto Institute of Oncology IOV–IRCCSVeneto Institute of Oncology IOV–IRCCSPharmacy Department, Academic HospitalPharmacy Department, Academic HospitalNeurosurgery Unit, Azienda Ospedaliera di PadovaDepartment of Medicine, Section of Immunology, University of VeronaUniv Lyon, Université Claude Bernard Lyon 1, CNRS, LAGEPP UMR 5007Veneto Institute of Oncology IOV–IRCCSAbstract Background Myeloid derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are two of the major players involved in the inhibition of anti-tumor immune response in cancer patients, leading to poor prognosis. Selective targeting of myeloid cells has therefore become an attractive therapeutic strategy to relieve immunosuppression and, in this frame, we previously demonstrated that lipid nanocapsules (LNCs) loaded with lauroyl-modified gemcitabine efficiently target monocytic MDSCs in melanoma patients. In this study, we investigated the impact of the physico-chemical characteristics of LNCs, namely size and surface potential, towards immunosuppressive cell targeting. We exploited myeloid cells isolated from glioblastoma patients, which play a relevant role in the immunosuppression, to demonstrate that tailored nanosystems can target not only tumor cells but also tumor-promoting cells, thus constituting an efficient system that could be used to inhibit their function. Results The incorporation of different LNC formulations with a size of 100 nm, carrying overall positive, neutral or negative charge, was evaluated on leukocytes and tumor-infiltrating cells freshly isolated from glioblastoma patients. We observed that the maximum LNC uptake was obtained in monocytes with neutral 100 nm LNCs, while positively charged 100 nm LNCs were more effective on macrophages and tumor cells, maintaining at low level the incorporation by T cells. The mechanism of uptake was elucidated, demonstrating that LNCs are incorporated mainly by caveolae-mediated endocytosis. Conclusions We demonstrated that LNCs can be directed towards immunosuppressive cells by simply modulating their size and charge thus providing a novel approach to exploit nanosystems for anticancer treatment in the frame of immunotherapy.http://link.springer.com/article/10.1186/s12951-020-00589-3Myeloid cellsLipid nanocapsulesGliomaMyeloid derived suppressor cellsImmunosuppression |
| spellingShingle | Laura Pinton Sara Magri Elena Masetto Marina Vettore Ilaria Schibuola Vincenzo Ingangi Ilaria Marigo Kevin Matha Jean-Pierre Benoit Alessandro Della Puppa Vincenzo Bronte Giovanna Lollo Susanna Mandruzzato Targeting of immunosuppressive myeloid cells from glioblastoma patients by modulation of size and surface charge of lipid nanocapsules Journal of Nanobiotechnology Myeloid cells Lipid nanocapsules Glioma Myeloid derived suppressor cells Immunosuppression |
| title | Targeting of immunosuppressive myeloid cells from glioblastoma patients by modulation of size and surface charge of lipid nanocapsules |
| title_full | Targeting of immunosuppressive myeloid cells from glioblastoma patients by modulation of size and surface charge of lipid nanocapsules |
| title_fullStr | Targeting of immunosuppressive myeloid cells from glioblastoma patients by modulation of size and surface charge of lipid nanocapsules |
| title_full_unstemmed | Targeting of immunosuppressive myeloid cells from glioblastoma patients by modulation of size and surface charge of lipid nanocapsules |
| title_short | Targeting of immunosuppressive myeloid cells from glioblastoma patients by modulation of size and surface charge of lipid nanocapsules |
| title_sort | targeting of immunosuppressive myeloid cells from glioblastoma patients by modulation of size and surface charge of lipid nanocapsules |
| topic | Myeloid cells Lipid nanocapsules Glioma Myeloid derived suppressor cells Immunosuppression |
| url | http://link.springer.com/article/10.1186/s12951-020-00589-3 |
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