Chitosan–Biotin-Conjugated pH-Responsive Ru(II) Glucose Nanogel: A Dual Pathway of Targeting Cancer Cells and Self-Drug Delivery

Abstract

The current study paves the way for improved chemotherapy by creating pH-responsive nanogels (NGs) (GC1 and GC2) loaded with synthetic ruthenium(II) arene complexes to increase biological potency. NGs are fabricated by the conjugation of chitosan (CTS)–biotin biopolymers that selectively target the cancer cells as CTS has the pH-responsive property, which helps in releasing the drug in cancer cells having pH ∼ 5.5, and biotin provides the way to target the cancer cells selectively due to the overexpression of integrin. The synthesized compounds and NGs were thoroughly characterized using various spectroscopic and analytical techniques such as NMR, electrospray ionization-mass spectrometry, Fourier transform infrared, UV–vis, scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, rheology, Brunauer–Emmett–Teller, and others. NGs displayed exceptional increased efficacy toward cancerous cells with IC50 values ranging from 7.50 to 18.86 μM via induced apoptosis in three human cancer cell lines. Apart from its potency, NGs were found to be highly selective toward cancer cells. Moreover, based on the results of immunoblot analysis, it was observed that the synthesized compounds exhibit a significant increase in the expression of cleaved caspase-3 and a decrease in the expression of the antiapoptotic protein BCL-XL. Interestingly, the complexes were discovered to have the additional capability of catalyzing the conversion of NADH to NAD+, leading to the generation of radical oxygen species within the cells. Additionally, it was discovered that NG-induced apoptosis depends on ROS production and DNA binding. A narrower range of LD50 values (1185.93 and 823.03 μM) was seen after administering NGs to zebrafish embryos in vivo. The results support the use of drug-loaded NGs as potential chemotherapeutic and chemopreventive agents for human cancer cells.

4″-Alkyl EGCG Derivatives Induce Cytoprotective Autophagy Response by Inhibiting EGFR in Glioblastoma Cells

“…The Western blot experiment was carried out as per the previously published reports from our group. ,, Briefly, after washing three times with 1X cold PBS, cells were lysed in RIPA buffer (1 M Tris pH 7.4, 2 M NaCl, 0.1 M EDTA, 1 M PMSF100 mM DTT, 1 mM sodium orthovanadate, Triton-X-100, glycerol and protease inhibitor cocktail, and phosphatase inhibitor cocktail) and collected. After centrifugation at 13,000 rpm for 20 min at 4 °C, the protein content was determined using a Bradford assay.…”

Design of an anticancer organoruthenium complex as the guest and polydiacetylene-coated fluorogenic nanocarrier as the host: engineering nanocarrier using ene-yne conjugation for sustained guest release, enhanced anticancer activity and reduced in vivo toxicity

“…In vivo zebrafish embryo toxicity (ZET) Zebrafish have been identified as a well-liked in vivo model for drug development and toxicity assessment in recent years due to their high degree of genetic resemblance to humans, rapid embryogenesis, short reproductive cycle, good transparency, and low cost. [62][63][64] Following the procedure reported to assess the in vivo ZET of ruthenium complexes 65 as well as OECD guidelines, 66 the hatching rate, survival rate, and malformations of zebrafish embryos exposed to Ru( pyr) and PDA-Ru ( pyr)@AMSNs were evaluated in different concentrations (10, 25, 50, 100, and 200 μM) at 24, 48, 72, and 96 hours after fertilization (Fig. 16A-C).…”

Improvement of the Antioxidant and Antitumor Activities of Benzimidazole-Chitosan Quaternary Ammonium Salt on Drug Delivery Nanogels

“…Several biodegradable polysaccharides, including chitosan and chitosan quaternary ammonium salts, have been extensively researched for the development of site-specific nanocarriers. These systems enable the targeted delivery of therapeutic agents exclusively to tumor sites [40][41][42]. Polysaccharide carriers exhibit great potential in the field of nanocarriers, offering beneficial biological properties such as antioxidant and antitumor effects.…”