Self-Immolative Polymers

School of Pharmacy, University of Nottingham, Nottingham, UK.
Angewandte Chemie International Edition (Impact Factor: 11.34). 09/2008; 47(41):7804-6. DOI: 10.1002/anie.200802474
Source: PubMed
1 Follower
  • [Show abstract] [Hide abstract]
    ABSTRACT: We recently reported the cationic polymerization of o-phthalaldehyde to macrocyclic poly(phthalaldehyde) polymers. Resubjecting the cyclic polymers to the polymerization conditions led to a redistribution of the polymer to a new cyclic structure consistent with thermodynamic equilibrium. We now report the synthesis of cyclic poly(phthalaldehyde) derivatives and demonstrate the scrambling of distinct homopolymer mixtures to copolymers under the cationic polymerization conditions. Homopolymer mixtures are found to rapidly redistribute, first to multiblock cyclic copolymers. With extended reaction time, random macrocyclic copolymers are obtained. Evolution of the microstructure was monitored by NMR spectroscopy, MALDI–TOF mass spectrometry, and gel permeation chromatography (GPC). The reported scrambling method leads to the rapid preparation of macrocyclic copolymers of high molecular weight with variable microstructure depending on reaction times and catalyst loadings.
    Macromolecules 10/2013; 46(20):8121–8128. DOI:10.1021/ma401744k · 5.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ultraviolet (UV) and near infrared (NIR) light-responsive polymeric nanomedicines (e.g., cargo-loaded micelles and vesicles) have increasingly received much attention for their applications in the spatiotemporal and on-demand drug delivery and disease therapy. This UV/NIR-sensitivity is activated via a one-photon and/or two-photon absorption process. The phototriggered micellar disruption and drug release have three mechanisms: (1) the hydrophobicity–hydrophilicity transition, (2) the photocleavage reaction, and (3) the cascade depolymerization reaction (e.g., self-immolative polymers). As NIR light can penetrate deeply into tissues (up to several inches) with less damage and scattering compared with UV and visible light, the polymeric nanomedicines simultaneously exhibiting both UV- and NIR-sensitivity hold great potential in clinical medicine and are especially discussed in this review.
    05/2013; 4(12):3431-3443. DOI:10.1039/C3PY21121E
  • [Show abstract] [Hide abstract]
    ABSTRACT: Poly(ester amide)s (PEAs) are of interest for a diverse range of applications as their structures and properties can be readily tuned through the incorporation of a wide variety of monomers. In this work, the incorporation of the amino acids L-2,4-diaminobutyric acid (DAB) and homocysteine (HCY) was investigated with the aim of imparting stimuli-responsive degradation properties to PEAs. First, small molecule model compounds were prepared and studied to demonstrate that upon revealing the pendant γ-amine or γ-thiol of DAB and HCY esters, intramolecular cyclizations to 5-membered lactams and thiolactones respectively were much more rapid than background ester hydrolysis. Subsequently, monomers containing these DAB and HCY self-immolative spacers were prepared and incorporated into PEAs such that cleavage of protecting groups on the pendant moieties by stimuli including acid and the reducing agent DTT induced cyclization reactions that directly cleaved esters in the PEA backbone. The degradation of these polymers both in solution and in films was studied, demonstrating stimuli-triggered degradation was more rapid than background polymer degradation. In addition, to demonstrate that the approach could be readily extended to various stimuli, a photochemically responsive PEA was prepared by simply changing the protecting group on the pendant amine. This intramolecular cyclization strategy involving pendant functional groups should therefore be useful for the development of a wide range of PEAs and other polymers for which it is desirable to initiate degradation under specified conditions.
    02/2013; 4(6):1969-1982. DOI:10.1039/C3PY21094D