Cancer-Targeted Chitosan–Biotin-Conjugated Mesoporous Silica Nanoparticles as Carriers of Zinc Complexes to Achieve Enhanced Chemotherapy In Vitro and In Vivo

Abstract

Despite being the most common component of numerous metalloenzymes in the human body, zinc complexes are still under-rated as chemotherapeutic agents. Herein, the present study opens up a key route toward enhanced chemotherapy with the help of two ZnII complexes (ZnMBC) synthesized alongside Mannich base ligands to upsurge biological potency. Further, well-established mesoporous silica nanoparticles (MSNs) have been chosen as carriers of the titled metallodrugs in order to achieve anticancer drug delivery. A pH-sensitive additive, namely, chitosan (CTS) conjugated with biotin is tagged to MSNs for the targeted release of core agents inside tumors selectively. In general, CTS blocks ZnMBC inside the mesopores of MSNs, and biotin acts as a targeting ligand to improve tumor-specific cellular uptake. CTS–biotin surface decoration significantly enhanced the cellular uptake of ZnMBC through endocytosis. A panel of four human cancer cell lines has revealed that ZnMBC (1/2)@MSNs–CTS–biotin nanoparticles (NPs) exhibits unprecedented enhanced cytotoxicity toward cancer cells with IC50 values ranging from 6.5 to 28.8 μM through induction of apoptosis. NPs also possess great selectivity between normal and cancer cells despite this potency. Two-photon-excited in vitro imaging of normal (HEK) and cancer (HeLa) cells has been performed to confirm the biased drug delivery. Also, NP-induced apoptosis was found to be dependent on targeting DNA and ROS generation. Moreover, a lower range of LD50 values (153.6–335.5 μM) were observed upon treatment zebrafish embryos with NPs in vivo. Because of the anatomical similarity to the human heart, the heart rate of NP-treated zebrafish has been analyzed in assessing the cardiac functions, which is in favor of the early clinical trials of ZnMBC (1/2)@MSNs–CTS–biotin candidates for their further evaluation as a chemotherapeutic and chemopreventive agent toward human cancers, especially adenocarcinoma.

Pyrene-based fluorescent Ru(ii)-arene complexes for significant biological applications: catalytic potential, DNA/protein binding, two photon cell imaging andin vitrocytotoxicity

“…Therefore, metastasis inhibition study is one of the foremost research areas of advanced cancer treatment. 30,31 For evaluating the effect of compounds on the migration capacity, HeLa cells were treated with complexes 1–4 at their IC 50 values and analysed for cell migration with time intervals. After 24 h of drug treatment, the treated cells show little or no migration at all in the scratched wound region while the PBS-treated cells (without drug treatment) showed significant migration to the scratched wound region (Fig.…”

A Novel Ibuprofen Derivative and Its Complexes: Physicochemical Characterization, DFT Modeling, Docking, In Vitro Anti-Inflammatory Studies, and DNA Interaction

“…So, the observed hyperchromic reflects structural damage, likely due to the complexes’ strong binding to the DNA base moieties through covalent-bond formation [ 55 , 68 , 69 , 70 ].…”

Studies on anticancer properties with varying co-ligands in a Ru(ii) arene benzimidazole system

“…The assay is founded upon the reduction of 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide or MTT (soluble) to formazan crystals (insoluble) by the enzymatic action of the mitochondria in viable cells. 51 While the ligand showed mild anticancer activity, all the complexes 1–3 exhibited potent cytotoxicity towards the MCF7 and HeLa cancerous cell lines, as revealed by the cell viability curves at different concentrations of the compounds (Fig. S22 and S23†).…”

“…The assay is founded upon the reduction of 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide or MTT (soluble) to formazan crystals (insoluble) by the enzymatic action of the mitochondria in viable cells. 51 While the ligand showed mild anticancer activity, all the complexes 1-3 exhibi-…”