Synthesis and properties of responsive hyaluronic acid micelles

doi:10.19491/j.issn.1001-9278.2024.07.005

Abstract

Abstract:

Hyaluronic acid （HA） is a natural polysaccharide with cancer cell targeting properties， and it can be used to construct polymeric nanocarriers sensitive to lesion environments based on special functional groups. Herein， the reversible addition⁃fragmentation chain transfer （RAFT） polymerization was used to synthesize a block copolymer of 3⁃acrylamide phenylboronic acid and vinyl pyrrolidone controllably. This block copolymer was self⁃assembled with hyaluronic acid through the borate ester bond to form nano⁃micelles. Adjusting the feeding concentration of two types of polymers and optimizing the chain length ratio of copolymers can obtain the regulation of micellar hydrodynamic diameter. When the concentration of copolymer was 7.5 mg/mL， the degree of polymerization was 40 and the molecular weight ratio of block was 2. The obtained particle size could be tunable from 73.3 to 163.9 nm， which is advantageous to long circulation in vivo and lesion penetration. The findings indicated that the nanoparticles had suitable pH， sugar， and salt responsiveness. In summary， a multi⁃responsive cancer cell targeting polymer nano⁃micelle has been synthesized in this study， and it exhibits great potential for applications as an antitumor drug and probe carrier.

Key words: hyaluronic acid, 3?acrylamide phenyl boronic acid, block copolymerization, responsiveness, nano micelle

CLC Number:

TQ320

LIU Chaofan, LIAO Shenglong, ZHONG Shuying, LIN Ying. Synthesis and properties of responsive hyaluronic acid micelles[J]. China Plastics, 2024, 38(7): 25-31.

Figures/Tables 11

Fig.1. Schematic of the preparation of PAPBA⁃b⁃PVP/HA micelles

Fig.2. 1H⁃NMR and FTIR spectra of APBA and PAPBA， as well as GPC curves of PAPBA

Fig.3. 1H⁃NMR spectra of PAPBA⁃b⁃PVP and FTIR spectra of PAPBA⁃b⁃PVP， NVP and PAPBA

Fig 4. GPC curves of PAPBA⁃b⁃PVP

Fig.5. Photo of PAPBA⁃b⁃PVP/HA micelles regulated by different HA concentrations and FTIR of HA， PAPBA⁃b⁃PVP and PAPBA⁃b⁃PVP/HA

Fig.6. Images and hydrodynamic diameter distribution of micelles with particle size of 142 nm and 156.2 nm，respectively

Fig.7. Hydrodynamic diameter changes of micelles with different block ratios and feed concentrations of the copolymer as a function of HA concentration

Fig.8. Effect of concentrations of reactants on the size of micelles and effect of the copolymer concentrations on micelle particle size and zeta potential at 3 mg/mL HA

Fig.9. Colloidal stability of nano micelles in media

Fig.10. The diameters and zeta potentials of nano micelles at different pH values

Fig.11. Effect of glucose and salt concentrations on the size of micelles and the sugar and salt responsive mechanism of micelles

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