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Progress in Chemistry 2022, Vol. 34 Issue (8): 1723-1733 DOI: 10.7536/PC220414 Previous Articles   Next Articles

• Review •

Synthesis, Properties and Applications of Enzyme-Responsive Linear-Dendritic Block Copolymers

Lijun Bao, Junwu Wei, Yangyang Qian, Yujia Wang, Wenjie Song, Yunmei Bi()   

  1. College of Chemistry and Chemical Engineering, Yunnan Normal University,Kunming 650500, China
  • Received: Revised: Online: Published:
  • Contact: Yunmei Bi
  • Supported by:
    National Natural Science Foundation of China(21564017)
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Linear-dendritic block copolymers (LDBCs) are composed of a linear polymer and dendrimers (dendrons). They not only combine the characteristics of the two types of polymers, but also have unique structures and properties. Furthermore, stimuli-responsive LDBCs can be generated through the selection and structural modification of their linear chains and dendrons. Stimuli-responsive LDBCs have attracted much attention in recent years because of combining the ability to respond to a specific stimulus and different polymeric architectures for a broad range of applications, including drug delivery, gene therapy and materials science. Among them, enzyme responsive LDBCs are able to specifically respond to endogenous enzymes. Compared with the polymers that are able to only respond to exogenous stimuli such as temperature, light, etc, enzyme responsive LDBCs have high selectivity and better biocompatibility. Therefore, they are more suitable for application in in vivo as biomedical materials. Amphiphilic enzyme responsive LDBCs are capable of self-assembling in aqueous solution into nano-aggregates and disassembling to release payloads upon enzymatic stimuli. Additionally, the self-assembly and enzyme responsive disassembly properties of amphiphilic enzyme responsive LDBCs can be adjusted by changing the enzyme-responsive groups, linear chains and dendrons of LDBCs. Due to their unique enzyme response properties and excellent biocompatibility, enzyme responsive LDBCs have broad application prospects in drug delivery, biomedical imaging, etc. Herein, this review summarizes the synthetic approaches of enzyme responsive LDBCs, the effect of the structures such as the length and structure of linear chain, and hydrophobicity of dendrons of the LDBCs on their self-assembly properties and enzyme-responsive properties. The applications of these copolymers are also introduced. Finally, the research prospect of enzyme responsive LDBCs are proposed.

Contents

1 Introduction

2 Synthetic approaches for enzyme responsive linear-dendritic block copolymers (LDBCs)

2.1 The divergent approach

2.2 The convergent approach

2.3 The coupling approach

3 Effect of LDBCs structures and enzyme concentration on the properties of enzyme responsive LDBCs

3.1 The effect of different enzyme responsive groups in the LDBCs

3.2 The effect of linear chain length of the LDBCs

3.3 The effect of linear chain structure and type of the LDBCs

3.4 The effect of hydrophobicity of dendrons in the LDBCs

3.5 The effect of enzyme concentration

4 Application of enzyme responsive LDBCs

4.1 As a drug carrier

4.2 Application in the field of fluorescent imaging probes

5 Conclusion and outlook

Key words: enzyme responsiveness, linear-dendritic block copolymers (LDBCs), synthetic approaches, structures and properties, drug carriers
Fig. 1 Structures of enzyme responsive LDBCs[11,22,23]
Fig. 2 Synthesis of enzyme responsive LDBCs PNVP-b-dendr(Phe-Lys)n (n =1~3) by a chain-first approach[11]
Fig. 3 Synthesis of enzyme responsive LDBCs (bis-MPA-Gn-b-PHEG (n = 1, 2) ) by a dendron-first approach[23]
Fig. 4 Synthesis of enzyme responsive LDBCs by a coupling approach[35]
Table 1 Enzyme responsive groups in LDBCs
LDBCs Response groups Enzyme ref
PEG-Dendron phenyl acetamide groups Penicillin G acylase (PGA) 22,37
PEG-Dendron ester groups Porcine liver esterase (PLE) 38
PEG、PEtOx or PAA-Dendron 35
PEG10kDa-dend-(Hex)4 and (PEG5 kDa)2-dend-(Hex)4 36
LD-DOX/Ce6 peptide bonds Cathepsin B 39
PNVCLn-b-D(Phe-Lys)1-3 (n=66,100) amide bonds and ester groups Papain 40
G-b-PHEG and PHEG-Gn-bis-MPA 23
PNVCL-b-Gn-Fmoc-Gly (n=1,2) 12
Fig. 5 Mechanism of disassembly of LDBCs micelles upon enzymatic activation[22]
Fig. 6 Effect of linear and V-shaped hydrophilic blocks on enzyme responsive disassembly properties of LDBC micelles[36]
Fig. 7 Enzyme-responsive release of LDBCs micelles loaded with hydrophobic small molecules in a covalent or non-covalent manner[52]
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