Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization-Induced Self-Assembly

Hao Sun; Wei Cao; Nanzhi Zang; Tristan D. Clemons; Georg M. Scheutz; Ziying Hu; Matthew P. Thompson; Yifei Liang; Maria Vratsanos; Xuhao Zhou; Wonmin Choi; Brent S. Sumerlin; Samuel I. Stupp; Nathan C. Gianneschi

doi:10.1002/anie.202006385

Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization-Induced Self-Assembly

Hao Sun, Wei Cao, Nanzhi Zang, Tristan D. Clemons, Georg M. Scheutz, Ziying Hu, Matthew P. Thompson, Yifei Liang, Maria Vratsanos, Xuhao Zhou, Wonmin Choi, Brent S. Sumerlin, Samuel I. Stupp, Nathan C. Gianneschi

Northwestern University

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Herein, we report the photoinitiated polymerization-induced self-assembly (photo-PISA) of spherical micelles consisting of proapoptotic peptide–polymer amphiphiles. The one-pot synthetic approach yielded micellar nanoparticles at high concentrations and at scale (150 mg mL⁻¹) with tunable peptide loadings up to 48 wt. %. The size of the micellar nanoparticles was tuned by varying the lengths of hydrophobic and hydrophilic building blocks. Critically, the peptide-functionalized nanoparticles imbued the proapoptotic “KLA” peptides (amino acid sequence: KLAKLAKKLAKLAK) with two key properties otherwise not inherent to the sequence: 1) proteolytic resistance compared to the oligopeptide alone; 2) significantly enhanced cell uptake by multivalent display of KLA peptide brushes. The result was demonstrated improved apoptosis efficiency in HeLa cells. These results highlight the potential of photo-PISA in the large-scale synthesis of functional, proteolytically resistant peptide–polymer conjugates for intracellular delivery.

Original language	English
Pages (from-to)	19136-19142
Number of pages	7
Journal	Angewandte Chemie - International Edition
Volume	59
Issue number	43
DOIs	https://doi.org/10.1002/anie.202006385
Publication status	Published - Oct 19 2020

Keywords

nanoparticles
peptide delivery
peptide–polymer conjugates
polymerization
scaled synthesis

ASJC Scopus subject areas

Catalysis
Chemistry(all)

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10.1002/anie.202006385

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Sun, H., Cao, W., Zang, N., Clemons, T. D., Scheutz, G. M., Hu, Z., Thompson, M. P., Liang, Y., Vratsanos, M., Zhou, X., Choi, W., Sumerlin, B. S., Stupp, S. I., & Gianneschi, N. C. (2020). Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization-Induced Self-Assembly. Angewandte Chemie - International Edition, 59(43), 19136-19142. https://doi.org/10.1002/anie.202006385

Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization-Induced Self-Assembly. / Sun, Hao; Cao, Wei; Zang, Nanzhi; Clemons, Tristan D.; Scheutz, Georg M.; Hu, Ziying; Thompson, Matthew P.; Liang, Yifei; Vratsanos, Maria; Zhou, Xuhao; Choi, Wonmin; Sumerlin, Brent S.; Stupp, Samuel I.; Gianneschi, Nathan C.

In: Angewandte Chemie - International Edition, Vol. 59, No. 43, 19.10.2020, p. 19136-19142.

Research output: Contribution to journal › Article › peer-review

Sun, H, Cao, W, Zang, N, Clemons, TD, Scheutz, GM, Hu, Z, Thompson, MP, Liang, Y, Vratsanos, M, Zhou, X, Choi, W, Sumerlin, BS, Stupp, SI & Gianneschi, NC 2020, 'Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization-Induced Self-Assembly', Angewandte Chemie - International Edition, vol. 59, no. 43, pp. 19136-19142. https://doi.org/10.1002/anie.202006385

Sun, Hao ; Cao, Wei ; Zang, Nanzhi ; Clemons, Tristan D. ; Scheutz, Georg M. ; Hu, Ziying ; Thompson, Matthew P. ; Liang, Yifei ; Vratsanos, Maria ; Zhou, Xuhao ; Choi, Wonmin ; Sumerlin, Brent S. ; Stupp, Samuel I. ; Gianneschi, Nathan C. / Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization-Induced Self-Assembly. In: Angewandte Chemie - International Edition. 2020 ; Vol. 59, No. 43. pp. 19136-19142.

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title = "Proapoptotic Peptide Brush Polymer Nanoparticles via Photoinitiated Polymerization-Induced Self-Assembly",

abstract = "Herein, we report the photoinitiated polymerization-induced self-assembly (photo-PISA) of spherical micelles consisting of proapoptotic peptide–polymer amphiphiles. The one-pot synthetic approach yielded micellar nanoparticles at high concentrations and at scale (150 mg mL−1) with tunable peptide loadings up to 48 wt. %. The size of the micellar nanoparticles was tuned by varying the lengths of hydrophobic and hydrophilic building blocks. Critically, the peptide-functionalized nanoparticles imbued the proapoptotic “KLA” peptides (amino acid sequence: KLAKLAKKLAKLAK) with two key properties otherwise not inherent to the sequence: 1) proteolytic resistance compared to the oligopeptide alone; 2) significantly enhanced cell uptake by multivalent display of KLA peptide brushes. The result was demonstrated improved apoptosis efficiency in HeLa cells. These results highlight the potential of photo-PISA in the large-scale synthesis of functional, proteolytically resistant peptide–polymer conjugates for intracellular delivery.",

keywords = "nanoparticles, peptide delivery, peptide–polymer conjugates, polymerization, scaled synthesis",

author = "Hao Sun and Wei Cao and Nanzhi Zang and Clemons, {Tristan D.} and Scheutz, {Georg M.} and Ziying Hu and Thompson, {Matthew P.} and Yifei Liang and Maria Vratsanos and Xuhao Zhou and Wonmin Choi and Sumerlin, {Brent S.} and Stupp, {Samuel I.} and Gianneschi, {Nathan C.}",

note = "Funding Information: The authors are grateful for the support of the NIH through the NHLBI (R01HL139001), National Science Foundation fund grants (DMR-1710105 and DMR-1904631), and an AFOSR MURI (FA9550-16-0150). Additional support was provided by the Center for Regenerative Nanomedicine in the Simpson Querrey Institute at Northwestern University. TDC acknowledges the support from an American Australian Association Dow Chemical Company Fellowship.",

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AU - Cao, Wei

AU - Zang, Nanzhi

AU - Clemons, Tristan D.

AU - Scheutz, Georg M.

AU - Hu, Ziying

AU - Thompson, Matthew P.

AU - Liang, Yifei

AU - Vratsanos, Maria

AU - Zhou, Xuhao

AU - Choi, Wonmin

AU - Sumerlin, Brent S.

AU - Stupp, Samuel I.

AU - Gianneschi, Nathan C.

N1 - Funding Information: The authors are grateful for the support of the NIH through the NHLBI (R01HL139001), National Science Foundation fund grants (DMR-1710105 and DMR-1904631), and an AFOSR MURI (FA9550-16-0150). Additional support was provided by the Center for Regenerative Nanomedicine in the Simpson Querrey Institute at Northwestern University. TDC acknowledges the support from an American Australian Association Dow Chemical Company Fellowship.

PY - 2020/10/19

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N2 - Herein, we report the photoinitiated polymerization-induced self-assembly (photo-PISA) of spherical micelles consisting of proapoptotic peptide–polymer amphiphiles. The one-pot synthetic approach yielded micellar nanoparticles at high concentrations and at scale (150 mg mL−1) with tunable peptide loadings up to 48 wt. %. The size of the micellar nanoparticles was tuned by varying the lengths of hydrophobic and hydrophilic building blocks. Critically, the peptide-functionalized nanoparticles imbued the proapoptotic “KLA” peptides (amino acid sequence: KLAKLAKKLAKLAK) with two key properties otherwise not inherent to the sequence: 1) proteolytic resistance compared to the oligopeptide alone; 2) significantly enhanced cell uptake by multivalent display of KLA peptide brushes. The result was demonstrated improved apoptosis efficiency in HeLa cells. These results highlight the potential of photo-PISA in the large-scale synthesis of functional, proteolytically resistant peptide–polymer conjugates for intracellular delivery.

AB - Herein, we report the photoinitiated polymerization-induced self-assembly (photo-PISA) of spherical micelles consisting of proapoptotic peptide–polymer amphiphiles. The one-pot synthetic approach yielded micellar nanoparticles at high concentrations and at scale (150 mg mL−1) with tunable peptide loadings up to 48 wt. %. The size of the micellar nanoparticles was tuned by varying the lengths of hydrophobic and hydrophilic building blocks. Critically, the peptide-functionalized nanoparticles imbued the proapoptotic “KLA” peptides (amino acid sequence: KLAKLAKKLAKLAK) with two key properties otherwise not inherent to the sequence: 1) proteolytic resistance compared to the oligopeptide alone; 2) significantly enhanced cell uptake by multivalent display of KLA peptide brushes. The result was demonstrated improved apoptosis efficiency in HeLa cells. These results highlight the potential of photo-PISA in the large-scale synthesis of functional, proteolytically resistant peptide–polymer conjugates for intracellular delivery.

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