TY - JOUR
T1 - Sequential intracellular release of water-soluble cargos from Shell-crosslinked polymersomes
AU - Du, Fanfan
AU - Bobbala, Sharan
AU - Yi, Sijia
AU - Scott, Evan Alexander
N1 - Funding Information:
We would like to thank Dr. Jisheng Xiao and Dr. Jessica Hornick for their generous aid and helpful suggestion for CLSM imaging. The assistance from Jonathan Remis for cryoTEM observation is acknowledged. We acknowledge staff and instrumentation support from the Integrated Molecular Structure Education and Research Center, Structural Biology Facility, NU Atomic and Nanoscale Characterization Experimental Center, Robert H. Lurie Comprehensive Cancer Center Flow Cytometry Core, and Biological Imaging Facility at Northwestern University. This work was supported by the National Institutes of Health Director's New Innovator Award (grant no. 1DP2HL132390-01), the Louis A. Simpson & Kimberly K. Querrey Center for Regenerative Nanomedicine Regenerative Nanomedicine Catalyst Award. SAXS experiments were performed at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) located at Sector 5 of the Advanced Photon Source (APS). DND-CAT is supported by Northwestern University, E.I. DuPont de Nemours & Co., and The Dow Chemical Company. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357.
Funding Information:
We would like to thank Dr. Jisheng Xiao and Dr. Jessica Hornick for their generous aid and helpful suggestion for CLSM imaging. The assistance from Jonathan Remis for cryoTEM observation is acknowledged. We acknowledge staff and instrumentation support from the Integrated Molecular Structure Education and Research Center, Structural Biology Facility, NU Atomic and Nanoscale Characterization Experimental Center, Robert H. Lurie Comprehensive Cancer Center Flow Cytometry Core, and Biological Imaging Facility at Northwestern University . This work was supported by the National Institutes of Health Director's New Innovator Award (grant no. 1DP2HL132390-01 ), the Louis A. Simpson & Kimberly K. Querrey Center for Regenerative Nanomedicine Regenerative Nanomedicine Catalyst Award. SAXS experiments were performed at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) located at Sector 5 of the Advanced Photon Source (APS). DND-CAT is supported by Northwestern University , E.I. DuPont de Nemours & Co., and The Dow Chemical Company . This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357.
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/7/28
Y1 - 2018/7/28
N2 - Polymer vesicles, i.e. polymersomes (PS), present unique nanostructures with an interior aqueous core that can encapsulate multiple independent cargos concurrently. However, the sequential release of such co-loaded actives remains a challenge. Here, we report the rational design and synthesis of oxidation-responsive shell-crosslinked PS with capability for the controlled, sequential release of encapsulated hydrophilic molecules and hydrogels. Amphiphilic brush block copolymers poly(oligo(ethylene glycol) methyl ether methacrylate)-b-poly(oligo(propylene sulfide) methacrylate) (POEGMA-POPSMA) were prepared to fabricate PS via self-assembly in aqueous solution. As a type of unique drug delivery vehicle, the interior of the PS was co-loaded with hydrophilic molecules and water-soluble poly(N-isopropylacrylamide) (PNIPAM) conjugates. Due to the thermosensitivity of PNIPAM, PNIPAM conjugates within the PS aqueous interior underwent a phase transition to form hydrogels in situ when the temperature was raised above the lower critical solution temperature (LCST) of PNIPAM. Via control of the overall shell permeability by oxidation, we realized the sequential release of two water-soluble payloads based on the assumption that hydrogels have much smaller membrane permeability than that of molecular cargos. The ability to control the timing of release of molecular dyes and PNIPAM-based hydrogels was also observed within live cells. Furthermore, leakage of hydrogels from the PS was effectively alleviated in comparison to molecular cargos, which would facilitate intracellular accumulation and prolonged retention of hydrogels within the cell cytoplasm. Thus, we demonstrate that the integration of responsive hydrogels into PS with crosslinkable membranes provides a facile and versatile technique to control the stability and release of water-soluble cargos for drug delivery purposes.
AB - Polymer vesicles, i.e. polymersomes (PS), present unique nanostructures with an interior aqueous core that can encapsulate multiple independent cargos concurrently. However, the sequential release of such co-loaded actives remains a challenge. Here, we report the rational design and synthesis of oxidation-responsive shell-crosslinked PS with capability for the controlled, sequential release of encapsulated hydrophilic molecules and hydrogels. Amphiphilic brush block copolymers poly(oligo(ethylene glycol) methyl ether methacrylate)-b-poly(oligo(propylene sulfide) methacrylate) (POEGMA-POPSMA) were prepared to fabricate PS via self-assembly in aqueous solution. As a type of unique drug delivery vehicle, the interior of the PS was co-loaded with hydrophilic molecules and water-soluble poly(N-isopropylacrylamide) (PNIPAM) conjugates. Due to the thermosensitivity of PNIPAM, PNIPAM conjugates within the PS aqueous interior underwent a phase transition to form hydrogels in situ when the temperature was raised above the lower critical solution temperature (LCST) of PNIPAM. Via control of the overall shell permeability by oxidation, we realized the sequential release of two water-soluble payloads based on the assumption that hydrogels have much smaller membrane permeability than that of molecular cargos. The ability to control the timing of release of molecular dyes and PNIPAM-based hydrogels was also observed within live cells. Furthermore, leakage of hydrogels from the PS was effectively alleviated in comparison to molecular cargos, which would facilitate intracellular accumulation and prolonged retention of hydrogels within the cell cytoplasm. Thus, we demonstrate that the integration of responsive hydrogels into PS with crosslinkable membranes provides a facile and versatile technique to control the stability and release of water-soluble cargos for drug delivery purposes.
KW - Oxidation-responsive
KW - Polymersomes
KW - Self-assembly
KW - Sequential release
KW - Shell crosslinking
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U2 - 10.1016/j.jconrel.2018.03.027
DO - 10.1016/j.jconrel.2018.03.027
M3 - Article
C2 - 29601932
AN - SCOPUS:85048606117
VL - 282
SP - 90
EP - 100
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -