Biomorphic engineering of multifunctional polylactide stomatocytes toward therapeutic nano-red blood cells

Jingxin Shao, Imke A.B. Pijpers, Shoupeng Cao, David S. Williams, Xuehai Yan, Junbai Li, Loai K.E.A. Abdelmohsen (Corresponding author), Jan C.M. van Hest (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Morphologically discrete nanoarchitectures, which mimic the structural complexity of biological systems, are an increasingly popular design paradigm in the development of new nanomedical technologies. Herein, engineered polymeric stomatocytes are presented as a structural and functional mimic of red blood cells (RBCs) with multifunctional therapeutic features. Stomatocytes, comprising biodegradable poly(ethylene glycol)-block-poly(D,L-lactide), possess an oblate-like morphology reminiscent of RBCs. This unique dual-compartmentalized structure is augmented via encapsulation of multifunctional cargo (oxygen-binding hemoglobin and the photosensitizer chlorin e6). Furthermore, stomatocytes are decorated with a cell membrane isolated from erythrocytes to ensure that the surface characteristics matched those of RBCs. In vivo biodistribution data reveal that both the uncoated and coated nano-RBCs have long circulation times in mice, with the membrane-coated ones outperforming the uncoated stomatoctyes. The capacity of nano-RBCs to transport oxygen and create oxygen radicals upon exposure to light is effectively explored toward photodynamic therapy, using 2D and 3D tumor models; addressing the challenge presented by cancer-induced hypoxia. The morphological and functional control demonstrated by this synthetic nanosystem, coupled with indications of therapeutic efficacy, constitutes a highly promising platform for future clinical application.

LanguageEnglish
JournalAdvanced Science
DOIs
StateAccepted/In press - 1 Jan 2019

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erythrocytes
Blood
Erythrocytes
Cells
engineering
Oxygen
Nanosystems
oxygen
Therapeutics
Photodynamic therapy
Photosensitizing Agents
Photosensitizers
Hemoglobin
Biological systems
Cell membranes
cargo
Encapsulation
Ethylene Glycol
hypoxia
Photochemotherapy

Keywords

  • biomorphic engineering
  • cell-mimetic
  • erythrocytes
  • hypoxia
  • stomatocytes

Cite this

@article{27bdb1100f3b44f09e766b9f97e4cb1e,
title = "Biomorphic engineering of multifunctional polylactide stomatocytes toward therapeutic nano-red blood cells",
abstract = "Morphologically discrete nanoarchitectures, which mimic the structural complexity of biological systems, are an increasingly popular design paradigm in the development of new nanomedical technologies. Herein, engineered polymeric stomatocytes are presented as a structural and functional mimic of red blood cells (RBCs) with multifunctional therapeutic features. Stomatocytes, comprising biodegradable poly(ethylene glycol)-block-poly(D,L-lactide), possess an oblate-like morphology reminiscent of RBCs. This unique dual-compartmentalized structure is augmented via encapsulation of multifunctional cargo (oxygen-binding hemoglobin and the photosensitizer chlorin e6). Furthermore, stomatocytes are decorated with a cell membrane isolated from erythrocytes to ensure that the surface characteristics matched those of RBCs. In vivo biodistribution data reveal that both the uncoated and coated nano-RBCs have long circulation times in mice, with the membrane-coated ones outperforming the uncoated stomatoctyes. The capacity of nano-RBCs to transport oxygen and create oxygen radicals upon exposure to light is effectively explored toward photodynamic therapy, using 2D and 3D tumor models; addressing the challenge presented by cancer-induced hypoxia. The morphological and functional control demonstrated by this synthetic nanosystem, coupled with indications of therapeutic efficacy, constitutes a highly promising platform for future clinical application.",
keywords = "biomorphic engineering, cell-mimetic, erythrocytes, hypoxia, stomatocytes",
author = "Jingxin Shao and Pijpers, {Imke A.B.} and Shoupeng Cao and Williams, {David S.} and Xuehai Yan and Junbai Li and Abdelmohsen, {Loai K.E.A.} and {van Hest}, {Jan C.M.}",
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doi = "10.1002/advs.201801678",
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T1 - Biomorphic engineering of multifunctional polylactide stomatocytes toward therapeutic nano-red blood cells

AU - Shao,Jingxin

AU - Pijpers,Imke A.B.

AU - Cao,Shoupeng

AU - Williams,David S.

AU - Yan,Xuehai

AU - Li,Junbai

AU - Abdelmohsen,Loai K.E.A.

AU - van Hest,Jan C.M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Morphologically discrete nanoarchitectures, which mimic the structural complexity of biological systems, are an increasingly popular design paradigm in the development of new nanomedical technologies. Herein, engineered polymeric stomatocytes are presented as a structural and functional mimic of red blood cells (RBCs) with multifunctional therapeutic features. Stomatocytes, comprising biodegradable poly(ethylene glycol)-block-poly(D,L-lactide), possess an oblate-like morphology reminiscent of RBCs. This unique dual-compartmentalized structure is augmented via encapsulation of multifunctional cargo (oxygen-binding hemoglobin and the photosensitizer chlorin e6). Furthermore, stomatocytes are decorated with a cell membrane isolated from erythrocytes to ensure that the surface characteristics matched those of RBCs. In vivo biodistribution data reveal that both the uncoated and coated nano-RBCs have long circulation times in mice, with the membrane-coated ones outperforming the uncoated stomatoctyes. The capacity of nano-RBCs to transport oxygen and create oxygen radicals upon exposure to light is effectively explored toward photodynamic therapy, using 2D and 3D tumor models; addressing the challenge presented by cancer-induced hypoxia. The morphological and functional control demonstrated by this synthetic nanosystem, coupled with indications of therapeutic efficacy, constitutes a highly promising platform for future clinical application.

AB - Morphologically discrete nanoarchitectures, which mimic the structural complexity of biological systems, are an increasingly popular design paradigm in the development of new nanomedical technologies. Herein, engineered polymeric stomatocytes are presented as a structural and functional mimic of red blood cells (RBCs) with multifunctional therapeutic features. Stomatocytes, comprising biodegradable poly(ethylene glycol)-block-poly(D,L-lactide), possess an oblate-like morphology reminiscent of RBCs. This unique dual-compartmentalized structure is augmented via encapsulation of multifunctional cargo (oxygen-binding hemoglobin and the photosensitizer chlorin e6). Furthermore, stomatocytes are decorated with a cell membrane isolated from erythrocytes to ensure that the surface characteristics matched those of RBCs. In vivo biodistribution data reveal that both the uncoated and coated nano-RBCs have long circulation times in mice, with the membrane-coated ones outperforming the uncoated stomatoctyes. The capacity of nano-RBCs to transport oxygen and create oxygen radicals upon exposure to light is effectively explored toward photodynamic therapy, using 2D and 3D tumor models; addressing the challenge presented by cancer-induced hypoxia. The morphological and functional control demonstrated by this synthetic nanosystem, coupled with indications of therapeutic efficacy, constitutes a highly promising platform for future clinical application.

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