Self-Assembled Supramolecular Micelles with pH-Responsive Properties for More Effective Cancer Chemotherapy

Abstract

pH-Responsive hydrogen-bonded supramolecular micelles, composed of a water-soluble poly(ethylene glycol) polymer with two terminal sextuple hydrogen bonding groups, can spontaneously organize in aqueous media to give well-defined, uniformly sized spherical micelles. The supramolecular micelles exhibit a number of unique physical characteristics, such as interesting amphiphilic behavior, desirable micellar size and nanospherical morphology, excellent biocompatibility, tailorable drug-loading capacities, and high structural stability in media containing serum or red blood cells. In addition, the drug release kinetics of drug-loaded micelles can be easily manipulated to achieve the desired release profile by regulating the environmental pH, thus these micelles are highly attractive candidates as an intelligent drug carrier system for cancer therapy. Cytotoxicity assays showed that the drug-loaded micelles induced pH-dependent intracellular drug release and exerted strong antiproliferative and cytotoxic activities toward cancer cells. Importantly, cellular uptake and flow cytometric analyses confirmed that a mildly acidic intracellular environment significantly increased cellular internalization of the drug-loaded micelles and subsequent drug release in the cytoplasm and nucleus of cancer cells, resulting in more effective induction of apoptotic cell death. Thus, this system may provide an efficient route toward achieving the fundamental properties and practical realization of pHsensitive drug-delivery systems for chemotherapy.

Exploring the Application of Micellar Drug Delivery Systems in Cancer Nanomedicine

“…These pH sensitive micelles can use slight pH changes to modify the micelles’ biodistribution and their interactions with tissues and cells. These characteristics allow encapsulated drugs to circumvent issues, including nonspecific toxicity, insufficient tumor selectivity, and the emergence of multidrug resistance in tumor cells [ 140 , 141 ]. If the pH of the surrounding environment changes, protons will be absorbed by the block copolymer if it contains weak acidic groups or released if it has weak basic groups.…”

Nanoscale Drug Delivery Systems in Glioblastoma

“…Comparing to other types of DDS, PMs could act as solubilizing agents for the replacement of toxic solvents [ 131 ]. PMs with different morphologies (spherical [ 132 ], cylindrical [ 133 ], lamellar [ 134 ]) garner distinctive biological and pharmacokinetic properties, among which the spherical assembly micelles were extensively elaborated (Fig. 6 ).…”

Hydrogen‐Bonds‐Mediated Nanomedicine: Design, Synthesis, and Applications

“…In addition, thanks to the presence of the U‐DPy associated dimers within the H‐bonded micellar interior, the resulting H‐boned micelles exhibit remarkable DOX‐encapsulating ability and structural stability in serum‐containing environments. [ 110 ] On the other hand, adenine‐ends‐capped PPG (A‐PPG‐A) was developed [ 94 ] to encapsulate magnolol ( Figure ), a hydroxylated biphenyl natural compound isolated from Magnolia officinalis and considered as a promising therapeutic agent for clinic research. [ 111 ]…”