Thermo/redox/pH-triple sensitive poly(N-isopropylacrylamide-co-acrylic acid) nanogels for anticancer drug delivery

Abstract

Doxorubicin is effectively loaded into disulfide-crosslinked poly(N-isopropylacrylamide-co-acrylic acid) nanogels, which can be triggerably released in a heating or reducing acidic tumor microenvironment.

Self-assembly of pH-sensitive fluorinated peptide dendron functionalized dextran nanoparticles for on-demand intracellular drug delivery

“…Within the last decade, persistent efforts have been made in the development of stimuli-responsive drug delivery systems that can, when exposed to external stimuli, produce physicochemical changes that favor drug release at the target site. Depending on the target, typical biological stimuli have been exploited for triggered drug release including temperature [1], pH [2][3][4], magnetic field [5,6], redox potential [7][8][9], enzymes [10][11][12] or two parameters at the same time [13][14][15]. pH controlled release systems are particularly more interesting because we can find physiologically the pH gradients relevant for drug targeting.…”

Preparation of thermo/redox/pH‐stimulative poly(N‐isopropylacrylamide‐co‐N,N′‐dimethylaminoethyl methacrylate) nanogels and their DOX release behaviors

“…It is worth noting that the solid tumor sites and endosomal/lysosomal compartments have quite an acidic environment (pH 5.0–6.5) . This suggest that DOX release is supposed to be less toxic against normal tissues and can release more DOX drugs in solid tumorous extracellular and endosomal/lysosomal vesicles …”

“…The narrow LCST interval of PNIPAM is not conducive to its potential practical application in biomedical fields . Introducing a second hydrophilic monomer into PNIPAM by free radical polymerization can adjust the LCST of the polymer to some extent . Methods usually used in the past for drug delivery applications still remain the pendant problems.…”

Polymer-based drug delivery systems for cancer treatment

“…The disulfide bond (‐SS‐) that widely exists in a variety of biological and chemical agents can be elegantly applied in the synthesis of reducible polymers . There're two commonly used synthetic methods to incorporate the disulfide bond into polymers: one is to directly introduce internal disulfide bond‐containing linkages such as cross‐linkers and living or controlled polymerization initiators; the other method is to introduce thiol‐containing or generated groups into polymers, in this case, a thiol‐disulfide exchange reaction will take place to turn thiol group into disulfide bond. According to the position of disulfide bond in polymers, ‐SS‐ linked NDDSs (‐SS‐ between hydrophilic and hydrophobic blocks), ‐SS‐ based cross‐linked NDDSs (core‐cross link or shell‐cross link by ‐SS‐), and ‐SS‐ based polymeric prodrug NDDSs (‐SS‐ between polymer and drug) can be masterly fabricated.…”