Thermal and enzymatic dual‐stimuli responsive linear‐dendritic block copolymers based on poly(N‐vinylcaprolactam)

Abstract

The first‐ and second‐generation well‐defined thermal and enzymatic dual‐stimuli responsive amphiphilic linear‐dendritic block copolymers (LDBCs) based on hydrophilic linear poly(N‐vinylcaprolactam) (PNVCL) and a hydrophobic Fmoc‐terminated dendron derived from an aliphatic polyester of 2, 2′‐dimethylolpropionic acid (bis‐MPA) have been synthesized via a combination of reversible addition fragmentation chain transfer (RAFT) polymerization of N‐vinylcaprolactam (NVCL) and “chain‐first” strategy. The copolymers were characterized by 1H NMR spectra and gel permeation chromatograph (GPC) analyses, showing controlled molecular weight and narrow molecular weight distribution (PDI ≤1.27). They self‐assemble in water into vesicles that are able to disrupt and release encapsulated cargos upon papain treatment. Their thermal‐responsive property was highly dependent on the generation and concentration of copolymers, and enzyme‐responsive behavior was affected by the generation of dendritic aliphatic polyester block. Moreover, papain influenced the thermal‐responsive behavior of the copolymers. Such smart copolymers could be efficiently used in drug delivery systems or biosensors.

Cathepsin B and thermal dual‐stimuli responsive linear‐dendritic block copolymer micelles for anticancer drug delivery

“…Synthesis of PNVCL n -NHBoc (n = 66, 100) With reference to the related literature, 22 Synthesis of PNVCL n -b-Phe-NHFmoc (n = 66, 100) To a solution of PNVCL 66 -NH 2 (3 g, 0.32 mmol), HOBt (0.043 g, 0.32 mmol), Fmoc-L-Phe-OH (0.37 g, 0.96 mmol) in 10 mL of dimethylformamide (DMF) was added DIC (0.12 g, 0.96 mmol). After stirring for 24 h at room temperature, the reaction mixture was subjected to precipitation by using ether.…”

“…The preparation of the copolymer solutions and the measurement of the transmittance were performed according to the literature. 22 Moreover, the copolymer solutions were treated with a cathepsin B stock solution (the final cathepsin B concentration was 0.37 U mL −1 and the copolymer solution concentration was 0.4 mg mL −1 ) at various time intervals (1, 2, 5, 12 and 24 h) to study the effect of the enzyme on the LCST behavior of these copolymers. The LCST values of PNVCL 100 -b-D(Phe-Lys) 3 in different concentrations of BSA were determined as a control.…”

“…These calibration errors were caused by using polystyrene standards, the hydrodynamic volume of which is quite different from the PNVCL polymer. 22…”

Enzyme and pH dual responsive linear-dendritic block copolymer micelles based on a phenylalanyl–lysine motif and peripherally ketal-functionalized dendron as potential drug carriers

“…Although many single stimulus responsive LDBCs have been obtained, dual responsive LDBCs have been relatively underexplored, especially systems that exhibit enzyme responsive behavior. 24,28,29 There are large variations in physiological conditions between normal microenvironments and diseased sites, thus single responsive polymer materials could not achieve the desired goals in a complex physiological microenvironment. The integration of several responsive moieties within one polymer is highly desired for biomedical applications.…”