Self-Assembled pH-Responsive Polymeric Micelles for Highly Efficient, Noncytotoxic Delivery of Doxorubicin Chemotherapy to Inhibit Macrophage Activation: In Vitro Investigation
Journal
Biomacromolecules
Journal Volume
19
Journal Issue
7
Pages
2772-2781
Date Issued
2018
Author(s)
Abstract
Self-assembled pH-responsive polymeric micelles, a combination of hydrophilic poly(ethylene glycol) segments and hydrogen bonding interactions within a biocompatible polyurethane substrate, can spontaneously self-assemble into highly controlled, nanosized micelles in aqueous solution. These newly developed micelles exhibit excellent pH-responsive behavior and biocompatibility, highly controlled drug (doxorubicin; DOX) release behavior, and high drug encapsulation stability in different aqueous environments, making the micelles highly attractive potential candidates for safer, more effective drug delivery in applications such as cancer chemotherapy. In addition, in vitro cell studies revealed the drug-loaded micelles possessed excellent drug entrapment stability and low cytotoxicity toward macrophages under normal physiological conditions (pH 7.4, 37 °C). When the pH of the culture media was reduced to 6.0 to mimic the acidic tumor microenvironment, the drug-loaded micelles triggered rapid release of DOX within the cells, which induced potent antiproliferative and cytotoxic effects in vitro. Importantly, fluorescent imaging and flow cytometric analyses confirmed the DOX-loaded micelles were efficiently delivered into the cytoplasm of the cells via endocytosis and then subsequently gradually translocated into the nucleus. Therefore, these multifunctional micelles could serve as delivery vehicles for precise, effective, controlled drug release to prevent accumulation and activation of tumor-promoting tumor-associated macrophages in cancer tissues. Thus, this unique system may offer a potential route toward the practical realization of next-generation pH-responsive therapeutic delivery systems. Copyright ? 2018 American Chemical Society.
Other Subjects
Biocompatibility; Chemical activation; Chemotherapy; Cytology; Cytotoxicity; Diseases; Encapsulation; Fluorescence imaging; Hydrogen bonds; Macrophages; Micelles; Molecular biology; Polyethylene glycols; Solutions; Targeted drug delivery; Tumors; Controlled drug release; Flow-cytometric analysis; Hydrogen bonding interactions; Macrophage activation; Physiological condition; Therapeutic delivery; Tumor associated macrophages; Tumor microenvironment; Controlled drug delivery; doxorubicin; macrogol; polymer; polyurethan; antineoplastic agent; doxorubicin; nanoparticle; antiproliferative activity; aqueous solution; Article; biocompatibility; cancer chemotherapy; cancer tissue; cell nucleus; chemical interaction; controlled drug release; controlled study; cytoplasm; drug cytotoxicity; drug delivery system; drug potency; drug stability; encapsulation; endocytosis; flow cytometry; hydrogen bond; hydrophilicity; in vitro study; macrophage activation; micelle; particle size; pH; priority journal; RAW 264.7 cell line; tumor associated leukocyte; tumor microenvironment; animal; chemistry; drug effect; drug release; macrophage activation; mouse; pH; Animals; Antineoplastic Agents; Doxorubicin; Drug Liberation; Endocytosis; Hydrogen-Ion Concentration; Macrophage Activation; Mice; Micelles; Nanoparticles; Polyethylene Glycols; Polyurethanes; RAW 264.7 Cells
Type
journal article