Novel ZnO hollow-nanocarriers containing paclitaxel targeting folate-receptors in a malignant pH-microenvironment for effective monitoring and promoting breast tumor regression

Abstract

Low pH in the tumor micromilieu is a recognized pathological feature of cancer. This attribute of cancerous cells has been targeted herein for the controlled release of chemotherapeutics at the tumour site, while sparing healthy tissues. To this end, pH-sensitive, hollow ZnO-nanocarriers loaded with paclitaxel were synthesized and their efficacy studied in breast cancer in vitro and in vivo. The nanocarriers were surface functionalized with folate using click-chemistry to improve targeted uptake by the malignant cells that over-express folate-receptors. The nanocarriers released ~75% of the paclitaxel payload within six hours in acidic pH, which was accompanied by switching of fluorescence from blue to green and a 10-fold increase in the fluorescence intensity. The fluorescence-switching phenomenon is due to structural collapse of the nanocarriers in the endolysosome. Energy dispersion X-ray mapping and whole animal fluorescent imaging studies were carried out to show that combined pH and folate-receptor targeting reduces off-target accumulation of the nanocarriers. Further, a dual cell-specific and pH-sensitive nanocarrier greatly improved the efficacy of paclitaxel to regress subcutaneous tumors in vivo. These nanocarriers could improve chemotherapy tolerance and increase anti-tumor efficacy, while also providing a novel diagnostic read-out through fluorescent switching that is proportional to drug release in malignant tissues.

Unique antitumor property of the Mg-Ca-Sr alloys with addition of Zn

“…In our previous study 20 , a series of quaternary Mg-Ca-Sr-Zn alloys were fabricated and the in vitro anti-bacterial property was conducted. Besides, in recent years, quit a few articles 21 22 reported that Zn 2+ selectively induced apoptosis in cancer cells 23 24 . Elevation of Zn 2+ concentration can trigger breakdown of mitochondrial membrane potential, caspase activation and cell apoptosis 25 .…”

Comparative analysis of the effect of low-dimensional alumina structures on cell lines L929 and Neuro-2a

“…Similar results of alumina nanostructure localization were obtained after incubation with L929 fibroblasts (data are not displayed). Thus, the synthesized nanostructures in the medium aggregate and cannot penetrate into the cell [31][32][33][34]. Their toxic effect is first of all related to changes in the cell microenvironment and interaction with the cell surface.…”

Cytotoxicity of biodegradable magnesium alloy WE43 to tumor cells in vitro: Bioresorbable implants with antitumor activity?

“…With an increase of the incubation time, the percentage of Annexin V(+) PI(+) cells increased, indicating the occurrence of late apoptosis. As mentioned above, the development of apoptosis in cells under the influence of metal ions can be due to a change in the mitochondrial membrane potential, activation of the caspase cycle, and suppression of MAPK activation . In addition, among the main triggers of cell apoptosis include oxidative stress .…”

“…It was shown that Mg–1Ca–0.5Sr– x Zn ( x = 0, 2, 4, 6 mass %) alloys inhibit the proliferation, viability, cell cycle, migration, and invasion of U2OS cells. The effect was associated with Zn ions released into the culture medium during biocorrosion, which impede the proliferation of tumor cells by changing the cell cycle and inducing cell apoptosis, mediated changes in the mitochondrial membrane potential, and activation of the caspase cell cycle . In addition, the ability of these tumor cells to migrate into the tissue is diminished through the inhibition of mitogen‐activated protein kinase (MAPK) activation.…”