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.
| Original language | English |
|---|---|
| Article number | 1901849 |
| Number of pages | 8 |
| Journal | Small |
| Volume | 15 |
| Issue number | 38 |
| DOIs | |
| Publication status | Published - 1 Sep 2019 |
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Keywords
- drug delivery
- nanomedicine
- nanostructures
- self-assembly
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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, 01.09.2019.Research output: Contribution to journal › Article › Academic › peer-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 - 2019/9/1
Y1 - 2019/9/1
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
C2 - 31379132
AN - SCOPUS:85070192334
VL - 15
JO - Small
JF - Small
SN - 1613-6810
IS - 38
M1 - 1901849
ER -