Dual Biochemically Breakable Drug Carriers from Programmed Telechelic Homopolymers

Abstract

Well-defined hydrophilic telechelic dibromo poly­(triethylene glycol monomethyl ether acrylate)­s were prepared by single-electron transfer living radical polymerization employing a hydrophobic difunctional initiator containing acetal and disulfide linkages. Although the resulting homopolymers have low hydrophobic contents (<8.5 wt % of the entire structure), they are able to self-assemble in water into nanoscale micellelike particles via chain folding. Acetal and disulfide linkages were demonstrated to be “keystone” units for their dual stimuli-responsive behavior under biochemically relevant conditions. Their site-selective middle-chain cleavage under both acidic pH and reductive conditions splits the homopolymer into two equal-sized fragments and results in the breakdown of the nanoassemblies. The drug loading/delivery potential of these nanoparticles was investigated using curcumine combining in vitro drug release, cytotoxicity, and cellular uptake studies with human cancer cell lines (HT-29 and HeLa). Importantly, this strategy may be extended to prepare innovative nanoplatforms based on hydrophilic homopolymers or random copolymers for intelligent drug delivery.

Breathable Lignin Nanoparticles as Reversible Gas Swellable Nanoreactors

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a tremendous attention owing the possibility for "on demand" engineering employing functional groups able to sense external stimuli such as pH, [5][6][7][8][9] light, [10][11][12] enzymes [13,14], and gases. [15,16] Among the advantages of these advanced materials, the most remarkable ones are the possibility to precisely control their disassembly processes in a spatiotemporal fashion, [12] and the ability to promote morphological transformations.

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Weakly Acidic pH and Reduction Dual Stimuli-Responsive Gel Particles

“…The pH-responsive moieties of gel particles are available for intracellular delivery of drugs by a proton sponge effect that enables the effective endolysosomal escape of gel particles . Reductive stimuli responsiveness is also useful in designing intracellular delivery carriers because the intracellular concentration of GSH (1–10 mM) is 2–3 orders of magnitude higher than the extracellular concentration of GSH (1–10 μM). , The pH and reduction dual stimuli-responsive DDS carriers have been studied since they are a useful platform for cancer therapy owing to the fact that tumor cells and tissues have low pH and reducing environments. − Since the PDEA-CBA gel particles have both pH-responsive tertiary amino groups and reductively cleavable disulfide cross-links, they have potential applications as drug carriers for intracellular delivery . First, we investigated the cellular uptake of PDEA-CBA gel particles.…”

Biotin‐decorated redox‐responsive micelles from diselenide‐linked star‐shaped copolymers for the targeted delivery and controlled release of doxorubicin in cancer cells

“…The release of CAs from PMs can be triggered by external and/or internal stimuli such as pH, light, reduction, radiation, temperature, and redox signals. [24][25][26][27] To this end, various stimuli-responsive moieties are often incorporated into the unimers of PMs. Of these, dynamic covalent S-S, Se-Se, and Te-Te bonds that sense the difference between intracellular and extracellular redox potentials [glutathione (GSH) and H 2 O 2 ] were used to govern the release of payloads in the intracellular compartment of tumor tissues.…”

“…Once the PMs are internalized into tumor cells either through passive diffusion or receptor‐mediated endocytosis, the cargo can be released into the cytosol to effectively elicit the intended anticancer activities. The release of CAs from PMs can be triggered by external and/or internal stimuli such as pH, light, reduction, radiation, temperature, and redox signals 24–27 . To this end, various stimuli‐responsive moieties are often incorporated into the unimers of PMs.…”