Poly(l‐histidine)‐containing polymer bioconjugate hybrid materials as stimuli‐responsive theranostic systems

Abstract

For decades, researchers have aspired to develop materials for noninvasive treatment and monitoring of pathological conditions. Various organs, tissues, subcellular compartments, and their pathophysiological states can be characterized by their pH values. pH-dependent intracellular tumor targeting has received particular attention due to the unique acidic environment of the solid tumors created by physiological and metabolical abnormalities. Responsive nanocarriers, when exposed to these pH stimuli, respond quickly to the physicochemical changes by undergoing structural deformations, such as swelling and phase transition, which favors the drug release specifically at the diseased site. Recently, researchers have developed several new poly(L-histidine) (p(His))-based pH responsive systems for sustained drug release and molecular targeting. This review focuses on the p(His)-based pH responsive nanocarriers, which are utilized in biomedical applications such as anti-cancer drug delivery and nucleic acid delivery. V C 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40796.

Smart polymers in drug delivery systems on crossroads: Which way deserves following?

“…Poly(L-histidine) and similar polymers have been used also as hydrophobic blocks in the construction of amphiphilic diblock copolymer-based micellar and nanoparticulate drug delivery systems [112,114,115,117]. These systems form stable micelles after loading with hydrophobic drugs in neutral pH while in the acidic milieu of the tumor interstitial space or endosome they are protonized and hydrophilized (at the hydrophobic polybase part) leading to micelle disassembly and triggered drug release (see Fig.…”

“…The ability to escape endosomes with acidification is also called ''proton sponge'' effect [125]. Poly(L-histidine) [112][113][114][115][116][117] (see Fig. 6d for structure) has a physiologically suitable pK a of the imidazole moiety (ca 6.8) for this purpose.…”

“…Among other polymer types that hold promise in cancer therapy are cationic polymers with ionizable amine groups [112][113][114][115][116][117]. By controlling the pK a of the amine groups, these polymers can be made to deprotonate at pH 7.4 and protonate when the pH is slightly reduced to tumor extracellular pH or intracellular pH.…”

Development of pH‐sensitive nanogels for cancer treatment using crosslinked poly(aspartic acid‐graft‐imidazole)‐block‐poly(ethylene glycol)

“…Recently, poly(amino acid)‐based nanogels (NGs) such as poly( l ‐histidine)‐based NGs, poly( l ‐lysine)‐based NGs, and poly( l ‐aspartic acid)‐based NGs, poly( l ‐glutamic acid)‐ based NGs have been reported as novel smart nanocarriers with pH‐sensitive functionality. Chemical crosslinking among pH‐sensitive polymers is one method for manipulating the properties of the polymeric micelles .…”

Synthesis and characterization of pH-sensitive poly(itaconic acid)–poly(ethylene glycol)–folate–poly(l-histidine) micelles for enhancing tumor therapy and tunable drug release

“…Undoubtedly, poly(L-histidine) is a perfect material for the establishment of pH-sensitive polymeric carriers [29]. The imidazole ring of PHIS has lone pairs of electrons on the unsaturated nitrogen that endow it with pH-sensitive amphoteric properties [30].…”