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In this paper, poly(ε-caprolactone)-graft-carboxylic acid (P(α-C[sub 2]CL)) was prepared via a thio-bromo click reaction between mercaptosuccinic acid and poly(α-bromo-ε-caprolactone). It is readily soluble in aqueous solutions (pH 5.5-9.8) due to the presence of carboxylic groups in each repeating unit. A series of water-soluble P(α-C[sub 2]CL)-paclitaxel prodrugs with high drug contents (up to 41.4wt-%) was prepared by esterification. Meanwhile, methyl tetrazolium (MTT) assays showed that P(α-C[sub 2]CL)-paclitaxel prodrugs exhibited a high antitumour effect on A549 and MCF-7 cells. These prodrugs have appeared as a highly versatile and potent platform for cancer therapy. [ABSTRACT FROM AUTHOR]

A biodegradable amphiphilic block copolymer of methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) bearing pendant aldehyde groups was synthesised by a combination of ring-opening polymerisation and thio-bromo 'click' chemistry. The free aldehyde groups on the copolymer were reacted with hydrophobic payloads (p-methoxylaniline as a model drug) by a benzoic-imine linker, which was responsive to pH change. NMR, FTIR, and gel permeation chromatography analysis confirmed the copolymer structures. In vitro release studies revealed that under acid stimulus, hydrolysis of the benzoic-imine bond resulted in a rapid drug release. This new amphiphilic block copolymer is expected to have promising applications in biodegradable controlled drug delivery systems. A biodegradable amphiphilic block copolymer bearing pendant aldehyde groups was synthesised by a combination of ring-opening polymerisation and thio-bromo 'click' chemistry. The free aldehyde groups were reacted with hydrophobic payloads by a pH responsive benzoic-imine linker. This new amphiphilic block copolymer is expected to have promising applications in biodegradable controlled drug delivery systems. [ABSTRACT FROM AUTHOR]

A series of core−shell molecular bottlebrushes with helical polypeptide backbone and polylactide-b-poly(ethylene glycol) block copolymer side chains [PPLG-g-(PLA-b-PEG)] have been synthesized via a grafting-to method. The structurally well-defined side chains with low molecular weight distribution (PDI < 1.03) have been synthesized by ring-opening polymerization (ROP) of dl-lactides using PEG-OH macroinitiator and AlEt3catalyst. Postpolymerization modification by esterification enables the quantitative installation of an alkynyl functionality at the block polymer chain ends. Grafting of alkynyl-terminated PLA-b-PEG onto poly(γ-azidopropyl-l-glutamate) (PAPLG) via copper-mediated [2 3] alkyne−azide 1,3-dipolar cycloaddition yields the targeted molecular bottlebrushes with high grafting density under mild conditions. A combination of the Langmuir−Blodgett (LB) technique with atomic force microscopy (AFM) has allowed for direct imaging of the synthesized molecular brushes and characterization of their molecular weight (MW) distribution. The imaged individual macromolecules demonstrate a wormlike conformation with an average length shorter than the contour length of the backbone. In agreement with the AFM observations, circular dichroism (CD) studies of PPLG-g-(PLA-b-PEG) in aqueous solution reveal that all molecular bottlebrushes retain backbones with α-helical conformations in acidic or neutral conditions. Longer side chains destabilize the helical conformations due to enhanced steric hindrance. Temperature variation can cause partial and reversible unfolding of the helical backbones. The temperature effect is greatly diminished for the bottlebrushes with longer side chains. [ABSTRACT FROM AUTHOR]

A series of poly(γ-chloropropyl-l-glutamate) (PCPLG) with controlled polymer molecular weight (MW = 5−28 kg·mol−1) and molecular weight distribution (PDI = 1.16−1.26) have been prepared from hexamethyldisilazane (HMDS)-mediated ring-opening polymerization (ROP) of γ-chloropropyl-l-glutamic acid based N-carboxylanhydride (CP-NCA). CD, FTIR, and WAXS analysis reveal that the polymers adopt α-helical conformations both in solution and the solid state. Their helical surfaces can be readily decorated with functional moieties to confer desired properties, as demonstrated by the quantitative derivatization of the PCPLG side chains with azido functional groups that are amendable to “click” chemistry. Subsequent side-chain conjugation with mannose moieties via copper-mediated [2 3] alkyne−azide 1,3-dipolar cycloaddition affords water-soluble mannose−polypeptide conjugates with quantitative grafting efficiency occurring under mild conditions. CD analysis reveals that the mannose−polypeptide conjugates also retain α-helical conformations in aqueous solution. [ABSTRACT FROM AUTHOR]