α‑Cyclodextrin Interacts Close to Vinblastine Site of Tubulin and Delivers Curcumin Preferentially to the Tubulin Surface of Cancer Cell

Tubulin is the key cytoskeleton component, which plays a crucial role in eukaryotic cell division. Many anticancer drugs have been developed targeting the tubulin surface. Recently, it has been shown that few polyhydroxy carbohydrates perturb tubulin polymerization. Cyclodextrin (CD), a polyhydroxy carbohydrate, has been extensively used as the delivery vehicle for delivery of hydrophobic drugs to the cancer cell. However, interaction of CD with intracellular components has not been addressed before. In this Article, we have shown for the first time that α-CD interacts with tubulin close to the vinblastine site using molecular docking and Förster resonance energy transfer (FRET) experiment. In addition, we have shown that α-CD binds with intracellular tubulin/microtubule. It delivers a high amount of curcumin onto the cancer cell, which causes severe disruption of intracellular microtubules. Finally, we have shown that the inclusion complex of α-CD and curcumin (CCC) preferentially enters into the human lung cancer cell (A549) as compared to the normal lung fibroblast cell (WI38), causes apoptotic death, activates tumor suppressor protein (p53) and cyclin-dependent kinase inhibitor 1 (p21), and inhibits 3D spheroid growth of cancer cell

Mitochondria-Targeted New Blue Light-Emitting Fluorescent Molecular Probe

Discovery of a nontoxic fluorescent molecular probe to “light up” specific cellular organelles is extremely essential to understand dynamics of intracellular components. Here, we report a new nontoxic mitochondria-targeted linear bithiazole compound, containing trifluoroacetyl terminal groups, which emits intense blue fluorescence and stained mitochondria of various cells. Interestingly, the power of fluorescence is completely off when the bithiazole unit is stapled by a carbonyl bridge

Assembly of an Injectable Noncytotoxic Peptide-Based Hydrogelator for Sustained Release of Drugs

A new synthetic tripeptide-based hydrogel has been discovered at physiological pH and temperature. This hydrogel has been thoroughly characterized using different techniques including field emission scanning electron microscopic (FE-SEM) and high-resolution transmission electron microscopic (HR-TEM) imaging, small- and wide-angle X-ray diffraction analyses, FT-IR, circular dichroism, and rheometric analyses. Moreover, this gel exhibits thixotropy and injectability. This hydrogel has been used for entrapment and sustained release of an antibiotic vancomycin and vitamin B₁₂ at physiological pH and temperature for about 2 days. Interestingly, MTT assay of these gelator molecules shows almost 100% cell viability of this peptide gelator, indicating its noncytotoxicity

Apoferritin Nanocage Delivers Combination of Microtubule and Nucleus Targeting Anticancer Drugs

An ideal nano drug delivery agent must be potent enough to carry high dose of therapeutics and competent enough in targeting specific cell of interest, having adequate optimized physiochemical properties and biocompatibility. Carrying differentially polar therapeutics simultaneously will make them superior in their class. However, it is of enormous challenge to the researchers to find such a unique nanocarrier and to engineer all of the above-mentioned features into it. In this manuscript, we have shown for the first time that apoferritin (Apf) can carry and deliver high dose of doxorubicin (Dox), docetaxel (Doc), and combination of both Dox and Doc specifically into the cancer cell and enhances killing compared to free drug without any functionalization or property modulation. In addition, we have shown that Apf alone is noncytotoxic in nature and interacts with intracellular tubulin/microtubule. Drug loaded Apf specifically bound and consequently internalized into the human breast cancer cell line (MCF7) and human cervical cancer cell line (HeLa) through receptor mediated endocytosis process and releases either single or combination of drugs in the endosome. We have also checked the binding efficacy of both drugs using molecular docking. Further, using fluorescence microscopy, we have shown that Apf can deliver combination of drugs inside cancer cells and the drugs exerts their effect thereof. Finally, we have studied the efficacy of Apf complexes with individual drugs and in combination compared to free drugs in a tumor mimicking 3D multicellular spheroid model of HeLa cell