Molecular programming of biodegradable nanoworms via ionically induced morphology switch toward asymmetric therapeutic carriers

Shoupeng Cao, Jingxin Shao, Yifeng Xia, Hailong Che, Zhiyuan Zhong, Fenghua Meng, Jan C.M. van Hest (Corresponding author), Loai K.E.A. Abdelmohsen (Corresponding author), David S. Williams

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Engineering biodegradable nanostructures with precise morphological characteristics is a key objective in nanomedicine. In particular, asymmetric (i.e., nonspherical) nanoparticles are desirable due to the advantageous effects of shape in a biomedical context. Using molecular engineering, it is possible to program unique morphological features into the self-assembly of block copolymers (BCPs). However, the criteria of biocompatibility and scalability limit progress due to the prevalence of nondegradable components and the use of toxic solvents during fabrication. To address this shortfall, a robust strategy for the fabrication of morphologically asymmetric nanoworms, comprising biodegradable BCPs, has been developed. Modular BCPs comprising poly (ethylene glycol)-block-poly(caprolactone-gradient-trimethylene carbonate) (PEG−PCLgTMC), with a terminal chain of quaternary ammonium-TMC (PTMC-Q), undergo self-assembly via direct hydration into well-defined nanostructures. By controlling the solution ionic strength during hydration, particle morphology switches from spherical micelles to nanoworms (of varying aspect ratio). This ionically-induced switch is driven by modulation of chain packing with salts screening interchain repulsions, leading to micelle elongation. Nanoworms can be loaded with cytotoxic cargo (e.g., doxorubicin) at high efficiency, preferentially interact with cancer cells, and increase tumor penetration. This work showcases the ability to program assembly of BCPs and the potential of asymmetric nanosystems in anticancer drug delivery.

LanguageEnglish
Article number1901849
Number of pages8
JournalSmall
Volume15
Issue number38
DOIs
StatePublished - 5 Aug 2019

Fingerprint

Nanostructures
Micelles
Block copolymers
Switches
Nanomedicine
Ethylene Glycol
Poisons
Ammonium Compounds
Hydration
Nanoparticles
Osmolar Concentration
Doxorubicin
Self assembly
Polyethylene glycols
Neoplasms
Program assemblers
Salts
Nanosystems
Medical nanotechnology
Fabrication

Keywords

  • drug delivery
  • nanomedicine
  • nanostructures
  • self-assembly

Cite this

@article{d6bf8e1901b44d0db77fcb7e058f4ca8,
title = "Molecular programming of biodegradable nanoworms via ionically induced morphology switch toward asymmetric therapeutic carriers",
abstract = "Engineering biodegradable nanostructures with precise morphological characteristics is a key objective in nanomedicine. In particular, asymmetric (i.e., nonspherical) nanoparticles are desirable due to the advantageous effects of shape in a biomedical context. Using molecular engineering, it is possible to program unique morphological features into the self-assembly of block copolymers (BCPs). However, the criteria of biocompatibility and scalability limit progress due to the prevalence of nondegradable components and the use of toxic solvents during fabrication. To address this shortfall, a robust strategy for the fabrication of morphologically asymmetric nanoworms, comprising biodegradable BCPs, has been developed. Modular BCPs comprising poly (ethylene glycol)-block-poly(caprolactone-gradient-trimethylene carbonate) (PEG−PCLgTMC), with a terminal chain of quaternary ammonium-TMC (PTMC-Q), undergo self-assembly via direct hydration into well-defined nanostructures. By controlling the solution ionic strength during hydration, particle morphology switches from spherical micelles to nanoworms (of varying aspect ratio). This ionically-induced switch is driven by modulation of chain packing with salts screening interchain repulsions, leading to micelle elongation. Nanoworms can be loaded with cytotoxic cargo (e.g., doxorubicin) at high efficiency, preferentially interact with cancer cells, and increase tumor penetration. This work showcases the ability to program assembly of BCPs and the potential of asymmetric nanosystems in anticancer drug delivery.",
keywords = "drug delivery, nanomedicine, nanostructures, self-assembly",
author = "Shoupeng Cao and Jingxin Shao and Yifeng Xia and Hailong Che and Zhiyuan Zhong and Fenghua Meng and {van Hest}, {Jan C.M.} and Abdelmohsen, {Loai K.E.A.} and Williams, {David S.}",
year = "2019",
month = "8",
day = "5",
doi = "10.1002/smll.201901849",
language = "English",
volume = "15",
journal = "Small",
issn = "1613-6810",
publisher = "Wiley-VCH Verlag",
number = "38",

}

Molecular programming of biodegradable nanoworms via ionically induced morphology switch toward asymmetric therapeutic carriers. / Cao, Shoupeng; Shao, Jingxin; Xia, Yifeng; Che, Hailong; Zhong, Zhiyuan; Meng, Fenghua; van Hest, Jan C.M. (Corresponding author); Abdelmohsen, Loai K.E.A. (Corresponding author); Williams, David S.

In: Small, Vol. 15, No. 38, 1901849, 05.08.2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Molecular programming of biodegradable nanoworms via ionically induced morphology switch toward asymmetric therapeutic carriers

AU - Cao,Shoupeng

AU - Shao,Jingxin

AU - Xia,Yifeng

AU - Che,Hailong

AU - Zhong,Zhiyuan

AU - Meng,Fenghua

AU - van Hest,Jan C.M.

AU - Abdelmohsen,Loai K.E.A.

AU - Williams,David S.

PY - 2019/8/5

Y1 - 2019/8/5

N2 - Engineering biodegradable nanostructures with precise morphological characteristics is a key objective in nanomedicine. In particular, asymmetric (i.e., nonspherical) nanoparticles are desirable due to the advantageous effects of shape in a biomedical context. Using molecular engineering, it is possible to program unique morphological features into the self-assembly of block copolymers (BCPs). However, the criteria of biocompatibility and scalability limit progress due to the prevalence of nondegradable components and the use of toxic solvents during fabrication. To address this shortfall, a robust strategy for the fabrication of morphologically asymmetric nanoworms, comprising biodegradable BCPs, has been developed. Modular BCPs comprising poly (ethylene glycol)-block-poly(caprolactone-gradient-trimethylene carbonate) (PEG−PCLgTMC), with a terminal chain of quaternary ammonium-TMC (PTMC-Q), undergo self-assembly via direct hydration into well-defined nanostructures. By controlling the solution ionic strength during hydration, particle morphology switches from spherical micelles to nanoworms (of varying aspect ratio). This ionically-induced switch is driven by modulation of chain packing with salts screening interchain repulsions, leading to micelle elongation. Nanoworms can be loaded with cytotoxic cargo (e.g., doxorubicin) at high efficiency, preferentially interact with cancer cells, and increase tumor penetration. This work showcases the ability to program assembly of BCPs and the potential of asymmetric nanosystems in anticancer drug delivery.

AB - Engineering biodegradable nanostructures with precise morphological characteristics is a key objective in nanomedicine. In particular, asymmetric (i.e., nonspherical) nanoparticles are desirable due to the advantageous effects of shape in a biomedical context. Using molecular engineering, it is possible to program unique morphological features into the self-assembly of block copolymers (BCPs). However, the criteria of biocompatibility and scalability limit progress due to the prevalence of nondegradable components and the use of toxic solvents during fabrication. To address this shortfall, a robust strategy for the fabrication of morphologically asymmetric nanoworms, comprising biodegradable BCPs, has been developed. Modular BCPs comprising poly (ethylene glycol)-block-poly(caprolactone-gradient-trimethylene carbonate) (PEG−PCLgTMC), with a terminal chain of quaternary ammonium-TMC (PTMC-Q), undergo self-assembly via direct hydration into well-defined nanostructures. By controlling the solution ionic strength during hydration, particle morphology switches from spherical micelles to nanoworms (of varying aspect ratio). This ionically-induced switch is driven by modulation of chain packing with salts screening interchain repulsions, leading to micelle elongation. Nanoworms can be loaded with cytotoxic cargo (e.g., doxorubicin) at high efficiency, preferentially interact with cancer cells, and increase tumor penetration. This work showcases the ability to program assembly of BCPs and the potential of asymmetric nanosystems in anticancer drug delivery.

KW - drug delivery

KW - nanomedicine

KW - nanostructures

KW - self-assembly

UR - http://www.scopus.com/inward/record.url?scp=85070192334&partnerID=8YFLogxK

U2 - 10.1002/smll.201901849

DO - 10.1002/smll.201901849

M3 - Article

VL - 15

JO - Small

T2 - Small

JF - Small

SN - 1613-6810

IS - 38

M1 - 1901849

ER -