Self-Assembled pH-Sensitive Polymeric Nanoparticles for the Inflammation-Targeted Delivery of Cu/Zn-Superoxide Dismutase

Xiangshi Sun; Kongtong Yu; Yulin Zhou; Shiyan Dong; Wenji Hu; Yating Sun; Yuhuan Li; Jing Xie; Robert J. Lee; Fengying Sun; Yifan Ma; Shengnian Wang; Betty Y.S. Kim; Yifan Wang; Zhaogang Yang; Wen Jiang; Youxin Li; Lesheng Teng

doi:10.1021/acsami.1c03589

Self-Assembled pH-Sensitive Polymeric Nanoparticles for the Inflammation-Targeted Delivery of Cu/Zn-Superoxide Dismutase

Xiangshi Sun, Kongtong Yu, Yulin Zhou, Shiyan Dong, Wenji Hu, Yating Sun, Yuhuan Li, Jing Xie, Robert J. Lee, Fengying Sun, Yifan Ma, Shengnian Wang, Betty Y.S. Kim, Yifan Wang, Zhaogang Yang, Wen Jiang, Youxin Li, Lesheng Teng

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

14 Scopus citations

Abstract

The use of superoxide dismutase (SOD) is currently limited by its short half-life, rapid plasma clearance rate, and instability. We synthesized a small library of biofriendly amphiphilic polymers that comprise methoxy poly(ethylene glycol)-poly(cyclohexane-1,4-diyl acetone dimethyleneketal) (mPEG-PCADK) and mPEG-poly((cyclohexane86.7%, 1,5-pentanediol13.3%)-1,4-diyl acetone dimethylene ketal) (PK3) for the targeted delivery of SOD. The novel polymers could self-assemble into micellar nanoparticles with favorable hydrolysis kinetics, biocompatibility, long circulation time, and inflammation-targeting effects. These materials generated a better pH-response curve and exhibited better hydrolytic kinetic behavior than PCADK and PK3. The polymers showed good biocompatibility with protein drugs and did not induce an acidic microenvironment during degradation in contrast to materials such as PEG-block-poly(lactic-co-glycolic acid) (PLGA) and PLGA. The SOD that contained reverse micelles based on mPEG2000-PCADK exhibited good circulation and inflammation-targeting properties. Pharmacodynamic results indicated exceptional antioxidant and anti-inflammatory activities in a rat adjuvant-induced arthritis model and a rat peritonitis model. These results suggest that these copolymers are ideal protein carriers for targeting inflammation treatment.

Original language	English (US)
Pages (from-to)	18152-18164
Number of pages	13
Journal	ACS Applied Materials and Interfaces
Volume	13
Issue number	15
DOIs	https://doi.org/10.1021/acsami.1c03589
State	Published - Apr 21 2021

Keywords

Cu/Zn-superoxide dismutase
drug delivery
nanoparticles
pH-sensitive
polyketals

ASJC Scopus subject areas

General Materials Science

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10.1021/acsami.1c03589

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Sun, X., Yu, K., Zhou, Y., Dong, S., Hu, W., Sun, Y., Li, Y., Xie, J., Lee, R. J., Sun, F., Ma, Y., Wang, S., Kim, B. Y. S., Wang, Y., Yang, Z., Jiang, W., Li, Y., & Teng, L. (2021). Self-Assembled pH-Sensitive Polymeric Nanoparticles for the Inflammation-Targeted Delivery of Cu/Zn-Superoxide Dismutase. ACS Applied Materials and Interfaces, 13(15), 18152-18164. https://doi.org/10.1021/acsami.1c03589

Sun, X, Yu, K, Zhou, Y, Dong, S, Hu, W, Sun, Y, Li, Y, Xie, J, Lee, RJ, Sun, F, Ma, Y, Wang, S, Kim, BYS, Wang, Y, Yang, Z, Jiang, W, Li, Y & Teng, L 2021, 'Self-Assembled pH-Sensitive Polymeric Nanoparticles for the Inflammation-Targeted Delivery of Cu/Zn-Superoxide Dismutase', ACS Applied Materials and Interfaces, vol. 13, no. 15, pp. 18152-18164. https://doi.org/10.1021/acsami.1c03589

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abstract = "The use of superoxide dismutase (SOD) is currently limited by its short half-life, rapid plasma clearance rate, and instability. We synthesized a small library of biofriendly amphiphilic polymers that comprise methoxy poly(ethylene glycol)-poly(cyclohexane-1,4-diyl acetone dimethyleneketal) (mPEG-PCADK) and mPEG-poly((cyclohexane86.7%, 1,5-pentanediol13.3%)-1,4-diyl acetone dimethylene ketal) (PK3) for the targeted delivery of SOD. The novel polymers could self-assemble into micellar nanoparticles with favorable hydrolysis kinetics, biocompatibility, long circulation time, and inflammation-targeting effects. These materials generated a better pH-response curve and exhibited better hydrolytic kinetic behavior than PCADK and PK3. The polymers showed good biocompatibility with protein drugs and did not induce an acidic microenvironment during degradation in contrast to materials such as PEG-block-poly(lactic-co-glycolic acid) (PLGA) and PLGA. The SOD that contained reverse micelles based on mPEG2000-PCADK exhibited good circulation and inflammation-targeting properties. Pharmacodynamic results indicated exceptional antioxidant and anti-inflammatory activities in a rat adjuvant-induced arthritis model and a rat peritonitis model. These results suggest that these copolymers are ideal protein carriers for targeting inflammation treatment.",

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author = "Xiangshi Sun and Kongtong Yu and Yulin Zhou and Shiyan Dong and Wenji Hu and Yating Sun and Yuhuan Li and Jing Xie and Lee, {Robert J.} and Fengying Sun and Yifan Ma and Shengnian Wang and Kim, {Betty Y.S.} and Yifan Wang and Zhaogang Yang and Wen Jiang and Youxin Li and Lesheng Teng",

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AU - Dong, Shiyan

AU - Hu, Wenji

AU - Sun, Yating

AU - Li, Yuhuan

AU - Xie, Jing

AU - Lee, Robert J.

AU - Sun, Fengying

AU - Ma, Yifan

AU - Wang, Shengnian

AU - Kim, Betty Y.S.

AU - Wang, Yifan

AU - Yang, Zhaogang

AU - Jiang, Wen

AU - Li, Youxin

AU - Teng, Lesheng

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AB - The use of superoxide dismutase (SOD) is currently limited by its short half-life, rapid plasma clearance rate, and instability. We synthesized a small library of biofriendly amphiphilic polymers that comprise methoxy poly(ethylene glycol)-poly(cyclohexane-1,4-diyl acetone dimethyleneketal) (mPEG-PCADK) and mPEG-poly((cyclohexane86.7%, 1,5-pentanediol13.3%)-1,4-diyl acetone dimethylene ketal) (PK3) for the targeted delivery of SOD. The novel polymers could self-assemble into micellar nanoparticles with favorable hydrolysis kinetics, biocompatibility, long circulation time, and inflammation-targeting effects. These materials generated a better pH-response curve and exhibited better hydrolytic kinetic behavior than PCADK and PK3. The polymers showed good biocompatibility with protein drugs and did not induce an acidic microenvironment during degradation in contrast to materials such as PEG-block-poly(lactic-co-glycolic acid) (PLGA) and PLGA. The SOD that contained reverse micelles based on mPEG2000-PCADK exhibited good circulation and inflammation-targeting properties. Pharmacodynamic results indicated exceptional antioxidant and anti-inflammatory activities in a rat adjuvant-induced arthritis model and a rat peritonitis model. These results suggest that these copolymers are ideal protein carriers for targeting inflammation treatment.

KW - Cu/Zn-superoxide dismutase

KW - drug delivery

KW - nanoparticles

KW - pH-sensitive

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ER -

Self-Assembled pH-Sensitive Polymeric Nanoparticles for the Inflammation-Targeted Delivery of Cu/Zn-Superoxide Dismutase

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