2 research outputs found
pH-Controlled Gas-Generating Mineralized Nanoparticles: A Theranostic Agent for Ultrasound Imaging and Therapy of Cancers
We report a theranostic nanoparticle that can express ultrasound (US) imaging and simultaneous therapeutic functions for cancer treatment. We developed doxorubicin-loaded calcium carbonate (CaCO<sub>3</sub>) hybrid nanoparticles (DOX-CaCO<sub>3</sub>-MNPs) through a block copolymer templated <i>in situ</i> mineralization approach. The nanoparticles exhibited strong echogenic signals at tumoral acid pH by producing carbon dioxide (CO<sub>2</sub>) bubbles and showed excellent echo persistence. <i>In vivo</i> results demonstrated that the DOX-CaCO<sub>3</sub>-MNPs generated CO<sub>2</sub> bubbles at tumor tissues sufficient for echogenic reflectivity under a US field. In contrast, the DOX-CaCO<sub>3</sub>-MNPs located in the liver or tumor-free subcutaneous area did not generate the CO<sub>2</sub> bubbles necessary for US contrast. The DOX-CaCO<sub>3</sub>-MNPs could also trigger the DOX release simultaneously with CO<sub>2</sub> bubble generation at the acidic tumoral environment. The DOX-CaCO<sub>3</sub>-MNPs displayed effective antitumor therapeutic activity in tumor-bearing mice. The concept described in this work may serve as a useful guide for development of various theranostic nanoparticles for US imaging and therapy of various cancers
Intracellular NO-Releasing Hyaluronic Acid-Based Nanocarriers: A Potential Chemosensitizing Agent for Cancer Chemotherapy
In
this work, we investigate whether <i>S</i>-nitrosoglutathione
(GSNO)-conjugated hyaluronic acid-based self-assembled nanoparticles
(GSNO-HANPs) can be useful as a chemosensitizing agent to improve
the anticancer activity of doxorubicin (DOX). The GSNO-HANPs were
prepared by aqueous assembly of GSNO-conjugated HA with grafted polyÂ(lactide-<i>co</i>-glycolide). Aqueous GSNO stability shielded within the
assembled environments of the GSNO-HANPs was greatly enhanced, compared
to that of free GSNO. The NO release from the GSNO-HANPs was facilitated
in the presence of hyaluronidase-1 (Hyal-1) and ascorbic acid at intracellular
concentrations. Microscopic analysis showed GSNO-HANPs effectively
generated NO within the cells. We observed that NO made the human
MCF-7 breast cancer cells vulnerable to DOX. This chemosensitizing
activity was supported by the observation of an increased level of
ONOO<sup>–</sup> (peroxynitrite), a highly reactive oxygen
species, upon co-treatment with the GSNO-HANPs and DOX. Apoptosis
assays showed that GSNO-HANP alone exhibited negligible cytotoxic
effects and reinforced apoptotic activity of DOX. Animal experiments
demonstrated the effective accumulation of GSNO-HANPs in solid MCF-7
tumors and effectively suppressed tumor growth in combination with
DOX. This hyaluronic acid-based intracellularly NO-releasing nanoparticles
may serve as a significant chemosensitizing agent in treatments of
various cancers