Enhanced cytotoxicity of a redox-sensitive hyaluronic acid-based nanomedicine toward different oncocytes via various internalization mechanisms

Abstract

Shen (2020) Enhanced cytotoxicity of a redox-sensitive hyaluronic acid-based nanomedicine toward different oncocytes via various internalization mechanisms, Drug Delivery, 27:1, 128-136, ABSTRACTReceptor-mediated active targeting and tumor microenvironment responsive systems from polymeric micelles have been studied for rapid cellular internalization and triggered drug release. Previously we have constructed redox-responsive polymeric micelles composed of vitamin E succinate conjugated hyaluronic acid (HA-ss-TOS), which are able to actively target CD44 proteins and quickly release loaded drugs upon exposure to high levels of glutathione (GSH) in tumor cells. In the present study, we found that despite different cellular internalization mechanisms, micelles showed strong antineoplastic effects on 4T1 and B16F10 cells due to redox responsiveness. HA-ss-TOS-PTX micelles exhibited an excellent tumor targeting ability and prolonged retention time compared to Taxol in vivo. In addition, a superior antitumor effect was achieved compared to PTX-loaded insensitive micelles (HA-TOS-PTX) and Taxol. Our results revealed that PTX-loaded HA-ss-TOS micelles could enhance the antineoplastic efficacy of PTX for breast cancer and melanoma treatment and, thus, deserve further attention. ARTICLE HISTORY

Hyaluronic Acid-modified Redox-sensitive Hybrid Nanocomplex Loading With siRNA for Non-small-cell Lung Carcinoma Therapy

“…2.4.3 Redox sensitivity of HA-SeSe-COOH/siR-93C@PAMAM HA-SeSe-COOH/siR-93C@PAMAM were treated with L-Glutathione (GSH concentration 10 nM or 20 µM) [18,31,32], H 2 O 2 (7.0 µmol/L or 1.0 mmol/L) [33][34][35][36][37], and normal saline, respectively. The particle size and the polydispersity index of ve groups were measured every 30 min to value the redox sensitivity of HA-SeSe-COOH/siR-93C@PAMAM.…”

“…Stimuli-triggered dis-shielding strategies have attracted enormous interest and boosted intense studies to improve the safety of PAMAM, redox-triggered dis-shielding is one of them, which is highly valued in cancer treatment. Compared with normal cells, most tumor cells exhibit higher levels of reactive oxygen species (ROS) and glutathione (GSH), it has been reported that the concentration of GSH in tumor tissues was at least 4-fold higher than that in normal tissues [17,18]. This unique redox environment of tumor allows the breakage of redox sensitive bonds to release loaded cargoes, for example disul de bonds [9,19,20].…”