Anti-cancer Activity of Biogenic Nat-ZnO Nanoparticles Synthesized Using Nyctanthes arbor-tristis (Nat) Flower Extract.

Inorganic nanoparticles (NPs) have played an important role as nano-drug delivery systems during cancer therapy in recent years. These NPs can carry cancer therapeutic agents. Due to this, they are considered a promising ancillary to traditional cancer therapies. Among inorganic NPs, Zinc Oxide (ZnO) NPs have been extensively utilized in cellular imaging, gene/drug delivery, anti-microbial, and anti-cancerous applications. In this study, a rapid and cost-effective method was used to synthesize Nat-ZnO NPs using the floral extract of the Nyctanthes arbor-tristis (Nat) plant. Nat-ZnO NPs were physicochemically characterized and tested further on in vitro cancer models. The average hydrodynamic diameter (Zaverage) and the net surface charge of Nat-ZnO NPs were 372.5 ± 70.38 d.nm and -7.03 ± 0.55 mV, respectively. Nat-ZnO NPs exhibited a crystalline nature. HR-TEM analysis showed the triangular shape of NPs. Furthermore, Nat-ZnO NPs were also found to be biocompatible and hemocompatible when tested on mouse fibroblast cells and RBCs. Later, the anti-cancer activity of Nat-ZnO NPs was tested on lung and cervical cancer cells. These NPs displayed potent anti-cancer activity and induced programmed cell death in cancer cells.

Organotypic cancer tissue models for drug screening: 3D constructs, bioprinting and microfluidic chips.

Successful translation of potential cancer chemotherapeutic drugs to the clinic depends on sufficient predictability of response in the human system through in vitro simulations. High expenditure and longer duration in preclinical and clinical research urge the enhancement of effective in vitro drug screening. 3D models emulate cell morphology, cell-cell and cell-matrix interactions and are physiologically more relevant for predicting drug responses for complex heterogenic cancers, widely replacing conventional cultures. Bioprinting and microfluidic technology facilitate tissue mimetic model construction and multifaceted simulation of physiology, respectively, promising more-appropriate predictability of drug interactions. Precisely, organotypic tissue constructs assembled using cell-laden matrices or organ-on-a-chip serve as realistic tissue models. This review projects the progress toward biomimetic tissue model development, highlighting the emergence of bioprinting and microfluidic technology in in vitro cancer drug screening and pertaining challenges.

Simulated microgravity increases polyploid giant cancer cells and nuclear localization of YAP.

Physical cues are vital in determining cellular fate in cancer. In vitro 3D culture do not replicate forces present in vivo. These forces including tumor interstitial fluid pressure and matrix stiffness behave as switches in differentiation and metastasis, which are intricate features of cancer stem cells (CSCs). Gravity determines the effect of these physical factors on cell fate and functions as evident from microgravity experiments on space and ground simulations. Here, we described the role of simulation of microgravity (SMG) using rotary cell culture system (RCCS) in increasing stemness in human colorectal cancer cell HCT116. We observed distinct features of cancer stem cells including CD133/CD44 dual positive cells and migration in SMG which was not altered by autophagy induction or inhibition. 3D and SMG increased autophagy, but the flux was staggered under SMG. Increased unique giant cancer cells housing complete nuclear localization of YAP were observed in SMG. This study highlights the role of microgravity in regulating stemness in CSC and importance of physical factors in determining the same.