Multi‐stimuli‐responsive self‐immolative polymer assemblies

Abstract

Self‐immolative polymers (SIPs) undergo depolymerization in response to the cleavage of stimuli‐responsive end‐caps from their termini. Some classes of SIPs, including polycarbamates, have depolymerization rates that depend on environmental factors such as solvent and pH. In previous work, hydrophobic SIPs have been incorporated into amphiphilic block copolymers and used to prepare nanoassemblies. However, stimuli‐responsive hydrophilic blocks have not previously been incorporated. In this work, we synthesized amphiphilic copolymers composed of a hydrophobic polycarbamate SIP block and a hydrophilic poly(2‐(dimethylamino)ethyl methacrylate) (PDMAEMA) block connected by a UV light‐responsive linker end‐cap. It was hypothesized that after assembly of the block copolymers into nanoparticles, chain collapse of the PDMAEMA above its lower critical solution temperature (LCST) might change the environment of the SIP block, thereby altering its depolymerization rate. Self‐assembly of the block copolymers was performed, and the depolymerization of the resulting assemblies was studied by fluorescence spectroscopy, dynamic light scattering, and NMR spectroscopy. At 20 °C, the system exhibited a selective response to the UV light. At 65 °C, above the LCST of PDMAEMA, the systems underwent more rapid depolymerization, suggesting that the increase in rate arising from the higher temperature dominated over environmental effects arising from chain collapse. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 1868–1877

Direct Visualization of Vesicle Disassembly and Reassembly Using Photocleavable Dendrimers Elucidates Cargo Release Mechanisms

“…Therefore, we combined high-power laser illumination and in situ visualization using confocal microscopy to directly observe photoinduced disassembly of a broad variety of giant dendrimersomes of distinct morphotypes and dynamic release of molecular and macromolecular cargos. We also observed spontaneous reassembly of lamellar and other nanoscale components, which may partially explain incomplete release of cargo from carriers reported by other laboratories. ,− ,, By leveraging the multilamellar structure of dendrimersomes and an NTA Janus dendrimer, we developed a generalizable optical cargo release and recruitment platform that can be readily functionalized with His-tagged proteins that are commonly available in bioscience laboratories. The physicochemical mechanisms that underlie the morphological transformation of these dendrimersomes upon photocleavage is an important area for future study.…”

“…We also observed spontaneous reassembly of lamellar and other nanoscale components, which may partially explain incomplete release of cargo from carriers reported by other laboratories. 30,[37][38][39][40][41][42]60,61 By leveraging the multilamellar structure of dendrimersomes and an NTA Janus dendrimer, we developed a generalizable optical cargo release and recruitment platform that can be readily functionalized with His-tagged proteins that are commonly available in bioscience laboratories. The physicochemical mechanisms that underlie the morphological transformation of these dendrimersomes upon photocleavage is an important area for future study.…”

Remote Light‐Responsive Nanocarriers for Controlled Drug Delivery: Advances and Perspectives

“…Based on the same strategy, Yardley and Gillies synthesized a self‐immolative amphiphilic copolymer containing an oNB linker end‐cap with a lower critical solution temperature (LCST) of 58 °C. Above the LCST, the polymeric micelles underwent more rapid degradation and drug release rate …”

“…Above the LCST, the polymeric micelles underwent more rapid degradation and drug release rate. [48] The photoinduced head-to-tail depolymerization strategy has been widely applied in the preparation of self-immolative dendrimers with prodrugs. [49] Shabat and co-workers developed a kind of carbamate-based self-immolative dendrimers containing Small 2019, 15,1903060 [38] Copyright 2018, American Chemical Society.…”

Stimulus-Responsive Nanomedicines for Disease Diagnosis and Treatment

“…A variety of similar structures based on nitrobenzyl groups can undergo self-immolation under UV light [ 197 , 198 ]. Examples of self-immolative structure triggered by NIR light are polymers with o-nitrobenzyl group as the capping group [ 199 , 200 ] and polymers based on coumarin derivatives [ 201 , 202 ].…”