Neural cell membrane-coated nanoparticles for targeted and enhanced uptake by central nervous system cells
Targeted drug delivery to specific neural cells within the central nervous system (CNS) plays important roles in treating neurological disorders, such as neurodegenerative (e.g. targeting neurons) and demyelinating diseases (e.g. targeting oligodendrocytes (OLs)). However, the presence of many other...
| Main Authors: | , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2021
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| Online Access: | https://hdl.handle.net/10356/153334 |
| _version_ | 1826110698647715840 |
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| author | Zhang, Na Lin, Junquan Chew, Sing Yian |
| author2 | School of Chemical and Biomedical Engineering |
| author_facet | School of Chemical and Biomedical Engineering Zhang, Na Lin, Junquan Chew, Sing Yian |
| author_sort | Zhang, Na |
| collection | NTU |
| description | Targeted drug delivery to specific neural cells within the central nervous system (CNS) plays important roles in treating neurological disorders, such as neurodegenerative (e.g. targeting neurons) and demyelinating diseases (e.g. targeting oligodendrocytes (OLs)). However, the presence of many other cell types within the CNS, such as microglial and astrocytes, may lead to non-specific uptake and subsequent side effects. As such, exploring an effective and targeted drug delivery system is of great necessity. Synthetic micro-/nano-particles that have been coated with biologically derived cellular membranes have emerged as a new class of drug delivery vehicles. However, the use of neural cell-derived membrane coatings remains unexplored. Here, we utilized this technique, and demonstrated the efficacy of targeted delivery by using four types of cell membranes that were derived from the CNS, namely microglial, astrocytes, oligodendrocyte progenitor cells (OPCs) and cortical neurons. Successful cell membrane coating over poly(-caprolactone) nanoparticles (NPs) was confirmed by dynamic light scattering (DLS), zeta potential measurements and transmission electron microscopy (TEM). Subsequently, an extensive screening of these cell membrane coated NPs was carried out on various CNS cells. Results suggested that microglial and OLs were the most sensitive cell types towards cell membrane coated NPs. Specifically, cell membrane coated NPs significantly enhanced the uptake efficiency of OLs (p < 0.001). Additionally, a temporal uptake study indicated that the OLs took up microglial membrane coated NPs (DPP-PCL-M Mem) most efficiently. Besides that, coating the NPs with four types of CNS cell membrane did not result in obvious specific uptake in microglial but reduced the activation of microglial, especially for DPP-PCL-M Mem (p < 0.01). Taken together, DPP-PCL-M Mem were uptaken most efficiently in OLs and did not induce significant microglial activation and may be most suitable for CNS drug delivery applications. |
| first_indexed | 2024-10-01T02:38:46Z |
| format | Journal Article |
| id | ntu-10356/153334 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:38:46Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1533342023-03-05T16:50:10Z Neural cell membrane-coated nanoparticles for targeted and enhanced uptake by central nervous system cells Zhang, Na Lin, Junquan Chew, Sing Yian School of Chemical and Biomedical Engineering Lee Kong Chian School of Medicine (LKCMedicine) Engineering::Chemical engineering Cell Membrane Coating Targeted Delivery Targeted drug delivery to specific neural cells within the central nervous system (CNS) plays important roles in treating neurological disorders, such as neurodegenerative (e.g. targeting neurons) and demyelinating diseases (e.g. targeting oligodendrocytes (OLs)). However, the presence of many other cell types within the CNS, such as microglial and astrocytes, may lead to non-specific uptake and subsequent side effects. As such, exploring an effective and targeted drug delivery system is of great necessity. Synthetic micro-/nano-particles that have been coated with biologically derived cellular membranes have emerged as a new class of drug delivery vehicles. However, the use of neural cell-derived membrane coatings remains unexplored. Here, we utilized this technique, and demonstrated the efficacy of targeted delivery by using four types of cell membranes that were derived from the CNS, namely microglial, astrocytes, oligodendrocyte progenitor cells (OPCs) and cortical neurons. Successful cell membrane coating over poly(-caprolactone) nanoparticles (NPs) was confirmed by dynamic light scattering (DLS), zeta potential measurements and transmission electron microscopy (TEM). Subsequently, an extensive screening of these cell membrane coated NPs was carried out on various CNS cells. Results suggested that microglial and OLs were the most sensitive cell types towards cell membrane coated NPs. Specifically, cell membrane coated NPs significantly enhanced the uptake efficiency of OLs (p < 0.001). Additionally, a temporal uptake study indicated that the OLs took up microglial membrane coated NPs (DPP-PCL-M Mem) most efficiently. Besides that, coating the NPs with four types of CNS cell membrane did not result in obvious specific uptake in microglial but reduced the activation of microglial, especially for DPP-PCL-M Mem (p < 0.01). Taken together, DPP-PCL-M Mem were uptaken most efficiently in OLs and did not induce significant microglial activation and may be most suitable for CNS drug delivery applications. Ministry of Education (MOE) National Research Foundation (NRF) Accepted version This work is supported by the National Research Foundation, Singapore, under its Intra-CREATE Thematic Grant Programme (NRF2019-THE002-0001) and the MOE Tier 1 grants (RG38/19 and RG37/20). 2021-12-13T13:21:26Z 2021-12-13T13:21:26Z 2021 Journal Article Zhang, N., Lin, J. & Chew, S. Y. (2021). Neural cell membrane-coated nanoparticles for targeted and enhanced uptake by central nervous system cells. ACS Applied Materials & Interfaces, 13(47), 55840-55850. https://dx.doi.org/10.1021/acsami.1c16543 1944-8244 https://hdl.handle.net/10356/153334 10.1021/acsami.1c16543 47 13 55840 55850 en NRF2019-THE002-0001 RG38/19 RG37/20 ACS Applied Materials & Interfaces This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Applied Materials & Interfaces, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsami.1c16543. application/pdf application/pdf |
| spellingShingle | Engineering::Chemical engineering Cell Membrane Coating Targeted Delivery Zhang, Na Lin, Junquan Chew, Sing Yian Neural cell membrane-coated nanoparticles for targeted and enhanced uptake by central nervous system cells |
| title | Neural cell membrane-coated nanoparticles for targeted and enhanced uptake by central nervous system cells |
| title_full | Neural cell membrane-coated nanoparticles for targeted and enhanced uptake by central nervous system cells |
| title_fullStr | Neural cell membrane-coated nanoparticles for targeted and enhanced uptake by central nervous system cells |
| title_full_unstemmed | Neural cell membrane-coated nanoparticles for targeted and enhanced uptake by central nervous system cells |
| title_short | Neural cell membrane-coated nanoparticles for targeted and enhanced uptake by central nervous system cells |
| title_sort | neural cell membrane coated nanoparticles for targeted and enhanced uptake by central nervous system cells |
| topic | Engineering::Chemical engineering Cell Membrane Coating Targeted Delivery |
| url | https://hdl.handle.net/10356/153334 |
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