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An injectable thermosensitive hydrogel self-supported by nanoparticles of PEGylated amino-modified PCL for enhanced local tumor chemotherapy

Abstract

We synthsized amino-modified poly(ε-caprolactone) PCN-b-PEG-b-PCN (PECN) triblock copolymers and studied the contribution of the introduced amino groups to the drug delivery efficiency of PECN nanoparticles (NPs) and their injectable thermosensitive hydrogels. PECN15 with the optimal amino group content was obtained. Firstly, the hydrophobic drug paclitaxel (PTX) loaded by PECN15 up to 5.91% and the formed PTX/PECN NPs with 90 nm in size and slightly positive charge (7.3 mV). Furthermore, the injectable PTX/PECN NPs aqueous solution (25 wt%) at ambient temperature could fast gelation at 37 oC and sustainedly release PTX/PECN NPs in 10 days. More importantly, comparing with our previous reported PECT NPs, the PECN NPs without increasing toxicity could improve the cell uptake and enhance the intracellular drug release by responding endosome acidic environment. Thus, PTX/PECN NPs presented lower IC50 of 3.14 μg mL-1 than that of PTX/PECT NPs (7.67 μg mL-1) and Free PTX (4.65 μg mL-1). Moreover, through peritumoral injection, the PTX/PECNGel showed 94.27% inhibition rate of tumor growth on day 19, higher than the PTX/PECTGel (72.28%) and Taxol® (47.03% ). Therefore, PECN NPs hydrogel provided a more significant injectable platform to enhance local cancer chemotherapy, and also provided further functionalization possibility by the reactive amino groups.

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Supplementary files

Article information


Submitted
24 Jan 2020
Accepted
17 May 2020
First published
18 May 2020

Soft Matter, 2020, Accepted Manuscript
Article type
Paper

An injectable thermosensitive hydrogel self-supported by nanoparticles of PEGylated amino-modified PCL for enhanced local tumor chemotherapy

J. Guo, Z. Feng, X. Liu, C. Wang, P. Huang, J. Zhang, L. Deng, W. Wang and A. Dong, Soft Matter, 2020, Accepted Manuscript , DOI: 10.1039/D0SM00147C

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