Metallic nanoparticles (MNPs) have been widely used for diagnostic and therapeutic purposes in clinical practice. A number of MNP formulations are being investigated in clinical trials for various applications. This increase in the use of NPs results in higher exposure to humans, leading to toxicity issues. Hence, it is necessary to determine the possible undesirable effects of the MNPs after in-vivo application and exposure. One of the main reasons for the toxicity of MNPs is the release of their respective metallic ions throughout the body. Many research studies are in progress investigating the various strategies to reduce the toxicity of MNPs. These research studies aim to change the size, dose, agglomeration, release, and excretion rates of MNPs. In this perspective review, we discussed the possible strategies to improve the therapeutic effects of MNPs through various processes, with lessons learned from the studies involving silver nanoparticles (AgNPs). We also discussed the ways to manage the toxicity of MNPs by purification, surface functionalization, synergistic effect, and targeted therapy approach. All these strategies could reduce the dose of the MNPs without compromising their therapeutic benefits, which could decrease the toxicity of MNPs. Additionally, we briefly discussed the market and toxicology testing for FDA-regulated MNPs.
Beta-Caryophyllene (BCP), a naturally occurring sesquiterpene abundantly found in cloves, hops, and cannabis, is the active candidate of a relatively new group of vascular-inhibiting compounds that aim to block existing tumor blood vessels. Previously, we have reported the anti-cancer properties of BCP by utilizing a series of in-vitro anti-tumor-related assays using human colorectal carcinoma cells. The present study aimed to investigate the effects of BCP on in-vitro, ex-vivo, and in-vivo models of anti-angiogenic assays and evaluate its anti-cancer activity in xenograft tumor (both ectopic and orthotopic) mice models of human colorectal cancer. Computational structural analysis and an apoptosis antibody array were also performed to understand the molecular players underlying this effect. BCP exhibited strong anti-angiogenic activity by blocking the migration of endothelial cells, tube-like network formation, suppression of vascular endothelial growth factor (VEGF) secretion from human umbilical vein endothelial cells and sprouting of rat aorta microvessels. BCP has a probable binding at Site#0 on the surface of VEGFR2. Moreover, BCP significantly deformed the vascularization architecture compared to the negative control in a chick embryo chorioallantoic membrane assay. BCP showed a remarkable reduction in tumor size and fluorescence molecular tomography signal intensity in all the mice treated with BCP, in a dose-dependent relationship, in ectopic and orthotopic tumor xenograft models, respectively. The histological analysis of the tumor from BCP-treated mice revealed a clear reduction of the density of vascularization. In addition, BCP induced apoptosis through downregulation of HSP60, HTRA, survivin, and XIAP, along with the upregulation of p21 expressions. These results suggest that BCP acts at multiple stages of angiogenesis and could be used as a promising therapeutic candidate to halt the growth of colorectal tumor cells.
Adenosine triphosphate (ATP) induced cell death (AICD) is a critical cellular process that has garnered substantial scientific interest for its profound relevance to cancer biology and to therapeutic interventions. This comprehensive review unveils the intricate web of AICD mechanisms and their intricate connections with cancer biology. This review offers a comprehensive framework for comprehending the multifaceted role of AICD in the context of cancer. This is achieved by elucidating the dynamic interplay between systemic and cellular ATP homeostasis, deciphering the intricate mechanisms governing AICD, elucidating its intricate involvement in cancer signaling pathways, and scrutinizing validated key genes. Moreover, the exploration of AICD as a potential avenue for cancer treatment underscores its essential role in shaping the future landscape of cancer therapeutics.