Dual-responsive Micelles Based on Boronicacid-modified Polymer†

doi:10.7503/cjcu20140270

Abstract

Abstract:

Phenylboronic acid modified polymer poly(ethylene glycol)-b-poly(aspartic acid-co-aspartamidophenylboronic acid)[PEG-b-P(Asp-co-AspPBA)] as well as a cross-linker 3,3'-dithiobis[1,2(S)-propanediol](DTBPD) which contained disulfide bond and dual-diol groups was successfully synthesized. PEG-b-P(Asp-co-AspPBA) could be mildly cross-linked by DTBPD based on the reaction of PBA and the dual-diol groups, leading to the formation of a novel dual-responsive micelle with boronic ester core and PEG shell. The structure, morphology, and the glucose/redox dual-responsive behavior of the micelles were systematically investigated by nuclear magnetic resonance(NMR) spectrum and dynamic laser light scattering(DLS). It was demonstrated that the ratio of diol to PBA(D∶B) had influence on the dual-responsive behavior of the micelles. At higher ratio of D∶B, only responsive swelling of micelles was observed. While for the micelles with lower ratio of D∶B, larger degree of swelling happened and the micelles gradually dissociated under higher concentrations of glucose ordithiothreitol(DTT). This kind of dual-responsive micelles may find application in drug delivery in the future.

Key words: Boronic acid, Disulfidebond, Cross-linked micelle, Glucose-response, Redox-response, Dual-responsive micelle

CLC Number:

O631

TrendMD:

SUN Xiaocheng, YANG Hao, WANG Jianzu, MA Rujiang, AN Yingli, SHI Linqi. Dual-responsive Micelles Based on Boronicacid-modified Polymer^†[J]. Chem. J. Chinese Universities, 2014, 35(7): 1570.

Figures/Tables 9

Scheme 1 Schematic illustration of DTBPD cross-linked micelles to response to glucose and DTT

Scheme 2 Synthesis routes of PEG-b-P(Asp-co-AspAPBA)

Scheme 3 Synthesis route of DTBPD

Fig.1 1H NMR spectra of PEG114-b-PBLA64 in CDCl3(a), PEG114-b-PAsp64 in D2O(b), PEG114-b-P(Asp37-co-AspAPBA27) in NaDO/D2O(c)

Fig.2 1H NMR spectra of α-thioglycerol(a) and DTBPD(b) in CD3OD

Fig.3 1H NMR spectra of DTBPD(a), PEG-b-P(Asp-co-AspAPBA)(b),PEG-b-P(Asp-co-AspAPB) micelles cross-linked by DTBPD in CD3OD(c)

Fig.4 Hydrodynamic size distributions as a function of the ratio of boronic acid [—B(OH)2] to diol(B∶D) with DTBPD as a cross-linker at a concentration of 0.2 mg/mL PEG-b-P(Asp-co-AspAPBA) in methanol solution(A) and TEM image of PEG-b-P(Asp-co-AspAPBA) micelles cross-linked by DTBPD at the B∶D ratio of 1∶1.5(B)

Fig.5 Hydrodynamic size distributions(A, C) and normalized light scattering intensity(B, D) of PEG-b-P(Asp-co-AspAPBA) micelles cross-linked by DTBPD at the B∶D ratios of 1∶3(A, B) and 1∶2(C, D) under various glucose concentrations in methanol solutions Concentration of glucose/(mg·mL-1): a. 0; b. 2; c. 5; d. 10.

Fig.6 Hydrodynamic size distributions(A, C) and normalized light scattering intensities(B, D) of PEG-b-P(Asp-co-AspAPBA) micelles cross-linked by DTBPD at the B∶D ratios of 1∶3(A, B) and 1∶2(C, D) under various DTT concentrations in methanol solutions Concentration of DTT/(mmol·L-1): a. 0; b. 2; c. 5; d. 10.

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