pH and Temperature Double-Switch Hybrid Micelles for Controllable Drug Release

Abstract

pH/temperature dual-responsive hybrid micelles were prepared for constructing a double-locked drug delivery system. The temperature-sensitive polyethylene glycol−poly-(tetrahydropyranylmethacrylate)−polyethylene glycol (PEG− PTHPMA−PEG) triblock copolymers were synthesized by reversible addition−fragmentation chain transfer polymerization and amide coupling reaction. pH-sensitive poly(2-(diisopropylamino ethylmethacrylate)−polyethylene glycol (PDPA−PEG) diblock polymers were introduced, which could self-assemble with PEG−PTHPMA−PEG in aqueous solutions to form hybrid micelles. The anticancer drug doxorubicin, which was encapsulated in the core of the hybrid micelles, could be released only under simultaneous stimulations of pH and temperature. It was proved that the micelles could maintain their structural stability under a unilateral stimulus, while the structure collapsed and recombined under a double stimulus, which triggered a large amount of drug release. Furthermore, the excellent biocompatibility and dual sensitivity of the vector were also proved by cytotoxicity experiments. The dual-responsive hybrid micelles designed here showed the advantages of a double insurance lock of drug leakage and precise controllability of drug release, which could act as accurate drug delivery systems.

Membrane Cargo Density-Dependent Interaction between Protein and Lipid Domains on the Giant Unilamellar Vesicles

“…We used the reconstitution approach with synthetic systems. − Reconstitution approach is advantageous in the sense that researchers can test physical models in a well-defined environment that can inspire them to design and synthesize biomimetic systems for therapeutic purposes. − In this study, we used bottom-up reconstitution with giant unilamellar vesicle (GUV) system, a lipid bilayer vesicle with a typical diameter of 1–100 μm. GUV has a relatively well-defined lipid composition and can be readily observed by optical microscopy.…”

Systematic Design and Study of Star-like Polymeric Prodrug Unimolecular Micelles β-CD-P[CL-co-(ACL-g-DOX)-SS-MPEG]21 by DPD Simulations

“…Nano-drug delivery system has been demonstrated to be a useful strategy for improving the therapeutic effect of anticancer drugs and reducing their side effects due to the existence of enhanced permeability and retention effect in tumor tissues. , Among them, nano-polymeric micelles assembled from amphiphilic polymers have shown unique advantages in enhancing the solubility of hydrophobic anticancer drugs and being easy to functionalize. − …”

Reactive Oxygen Species and Folate Receptor-Targeted Nanophotosensitizers Composed of Folic Acid-Conjugated and Poly(ethylene glycol)-Chlorin e6 Tetramer Having Diselenide Linkages for Targeted Photodynamic Treatment of Cancer Cells

“…On the other hand, nanocarrier-based drug delivery systems have been spotlighted in last several decades due to their superiority in drug targeting issues [ 17 , 18 , 19 , 20 , 21 ]. Due to their small size, nanocarriers are believed to be an ideal candidate for tumor targeting [ 17 , 18 ].…”

“…Since the surface of nanocarriers such as polymeric nanoparticles can be easily decorated with targeting moieties such as monoclonal antibodies, they can then be specifically delivered to the tumor with a minimization of side effects against normal cells [ 17 , 18 ]. Furthermore, nanocarriers based on polymeric nanoparticles or micelles can be designed to stimulate of tumor tissues and then deliver the anticancer drug to the tumor tissues specifically [ 18 , 19 , 20 , 21 ]. For example, Lei et al reported that polymeric micelles having pH and temperature dual-responsive properties accelerate the release rate of anticancer drugs at an acidic pH and a higher temperature [ 20 ].…”

“…Furthermore, nanocarriers based on polymeric nanoparticles or micelles can be designed to stimulate of tumor tissues and then deliver the anticancer drug to the tumor tissues specifically [ 18 , 19 , 20 , 21 ]. For example, Lei et al reported that polymeric micelles having pH and temperature dual-responsive properties accelerate the release rate of anticancer drugs at an acidic pH and a higher temperature [ 20 ]. From these points of view, stimuli-responsive nanocarriers have great potential in tumor targeting, because the physiological properties of the tumor microenvironment are quite different from their normal counterparts (i.e., tumor tissues are characterized as having an acidic pH, abnormal redox status, abundant extra- or intra-cellular enzymes and elevated expression of various molecular receptors) [ 22 , 23 , 24 , 25 ].…”