Matrix metalloproteinase-2 (MMP-2)-responsive nanodrug vehicles have garnered significant attention as antitumor drug delivery systems due to the extensive research on matrix metalloproteinases (MMPs) within the tumor extracellular matrix (ECM). These nanodrug vehicles exhibit stable circulation in the bloodstream and accumulate specifically in tumors through various mechanisms. Upon reaching tumor tissues, their structures are degraded in response to MMP-2 within the ECM, resulting in drug release. This controlled drug release significantly increases drug concentration within tumors, thereby enhancing its antitumor efficacy while minimizing side effects on normal organs. This review provides an overview of MMP-2 characteristics, enzyme-sensitive materials, and current research progress regarding their application as MMP-2-responsive nanodrug delivery system for anti-tumor drugs, as well as considering their future research prospects. In conclusion, MMP-2-sensitive drug delivery carriers have a broad application in all kinds of nanodrug delivery systems and are expected to become one of the main means for the clinical development and application of nanodrug delivery systems in the future.

Melatonin is a neuroendocrine hormone secreted by the pineal gland. The secretion of melatonin follows a circadian rhythm controlled by the suprachiasmatic nucleus, and its secretion is synchronized with the changes in light and dark periods in nature, with the highest secretion level at night. Melatonin is a critical hormone that coordinates external light stimulation and cellular responses of the body. It transmits information about the environmental light cycle, including the circadian and seasonal rhythms, to the relevant tissues and organs in the body, which, along with changes in its secretion level, ensures that its regulated functional activities are adapted in response to changes in the outside environment. Melatonin takes beneficial actions mainly through the interaction with specific membrane-bound receptors, termed MT1 and MT2. Melatonin also acts as a scavenger of free radicals via non-receptor-mediated mechanism. For more than half of acentury melatonin has been associated with vertebrate reproduction, especially in the context of seasonal breeding. Though modern humans show little remaining reproductive seasonality, the relationships between melatonin and human reproduction continue to attract extensive attention. Melatonin plays important roles in improving mitochondrial function, reducing the damage of free radicals, inducing oocyte maturation, increasing fertilization rate and promoting embryonic development, which improves the outcomes of in vitro fertilization and embryo transfer. The present article reviews the progress that has been made in our evolving understanding of the physiological role of melatonin in reproduction and its potential clinical applications in reproductive medicine.

UNASSIGNED: To provide a systematic review of existing meta-analysis on the efficacy, safety and pharmacokinetics of the novel Polo-like kinase-1 (Plk1) inhibitors in various tumor treatments, and assess the methodological quality and the strength of evidence of the included meta-analysis.
UNASSIGNED: The Medline, PubMed, Embase, etc. were searched and updated on 30 June 2022. 22 eligible clinical trials involving a total of 1256 patients were included for analyses. Randomised controlled trials (RCTs) compared the efficacy or safety, or both of any Plk1 inhibitors with placebo (active or inert) in participants. To be included, studies had to be RCTs, quasi-RCTs, and nonrandomized comparative studies.
UNASSIGNED: A meta-analysis of two trials reported progression-free survival (PFS) of the overall population (effect size (ES), 1.01; 95% confidence intervals (CIs), 0.73-1.30, I2 =0.0%, P<0.001) and overall survival (OS) of the overall population (ES, 0.91; 95% CIs, 0.31-1.50, I2 =77.6%, P=0.003). 18 adverse events (AEs) reflected that the possibility of occurrence of AEs in the Plk1 inhibitors group was 1.28 times higher than in the control group (odds ratios (ORs), 1.28; 95% CIs,1.02-1.61). The results of meta-analysis showed that the incidence of AEs in the nervous system was the highest (ES, 0.202; 95% CIs, 0.161-0.244), followed by blood system (ES, 0.190; 95% CIs, 0.178-0.201) and digestive system (ES, 0.181; 95% CIs, 0.150-0.213). Rigosertib (ON 01910.Na) was associated with a decreased risk of AEs in digestive system (ES, 0.103; 95% CIs, 0.059-0.147), but BI 2536 and Volasertib (BI 6727) increased risk of AEs in blood system (ES, 0.399; 95% CIs, 0.294-0.504). Five eligible studies reported the pharmacokinetic parameters of the low dosage (100 mg) cohort and the high dosage (200 mg) cohort, and there was no statistical difference in the total plasma clearance, terminal half-life and apparent volume of distribution at steady state.
UNASSIGNED: Plk1 inhibitors work better in improving OS and they are well tolerated, effective and safe in reducing the severity of illness while improving the quality of life, especially in patients with non-specific tumors, respiratory system tumors, musculoskeletal system tumors, and urinary system tumors. However, they fail to prolong the PFS. From the vertical whole level analysis, compared to other systems in the body, Plk1 inhibitors should be avoided as far as possible for the treatment of tumors related to the blood circulatory system, digestive system and nervous system, which were attributed to the intervention of Plk1 inhibitors associated with an increased risk of AEs in these systems. The toxicity caused by immunotherapy should be carefully considered. Conversely, a horizontal comparison of three different types of Plk1 inhibitors suggested that Rigosertib (ON 01910.Na) might be relatively suitable for the treatment of tumors associated with the digestive system, while Volasertib (BI 6727) might be even less suitable for the treatment of tumors associated with the blood circulation system. Additionally, in the dose selection of Plk1 inhibitors, the low dose of 100 mg should be preferred, and meanwhile, it can also ensure the pharmacokinetic efficacy that is indistinguishable from the high dose of 200 mg.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/, identifier CRD42022343507.

Antitumour treatments are evolving, including bacteria-mediated cancer therapy which is concurrently an ancient and cutting-edge approach. Salmonella typhimurium is a widely studied bacterial species that colonizes tumor tissues, showing oncolytic and immune system-regulating properties. It can be used as a delivery vector for genes and drugs, supporting conventional treatments that lack tumor-targeting abilities. This article summarizes recent evidence on the anticancer mechanisms of S. typhimurium alone and in combination with other anticancer treatments, suggesting that it may be a suitable approach to disease management.

Carbonic anhydrase IX (CAIX) is a transmembrane protein that is specifically overexpressed on the surface of hypoxic tumor cells. With the function of regulating the acidity of tumor cells both inside and outside, CAIX is closely related to tumor proliferation, invasion and metastasis. Therefore, CAIX is a promising target for tumor imaging and therapy. Herein, we summarized recent advances in CAIX-based tumor imaging, therapy and theranostics, and prospected future applications of using CAIX as an anti-tumor target.

UNASSIGNED: Cancer is an important disease and can occur anywhere in the body. It is caused by uncontrolled cell growth that spreads to other body parts. This study extensively investigated the transmembrane receptor tissue factor (TF), which is the key motivator of the clotting cascade and plays an essential role in cancer-associated coagulation. TF is considered to be aberrantly expressed in various tumors and appears to promote tumor angiogenesis and metastasis. Therefore, this study was performed to explain the pathological characteristics of TF expression and to discuss future cancer therapies that target TF.
UNASSIGNED: We extensively reviewed the literature on TF published in PubMed, and discussed the effect of TF on tumor progression and TF-targeted therapeutics.
UNASSIGNED: This review aimed to uncover how TFs contribute to tumor progression and cancer-associated thrombosis and summarize TF-based targeted therapy. Multiple functions and mechanisms of the TF in cancer-associated thrombosis and tumor progression were discussed.
UNASSIGNED: The current literature has confirmed that the TF is involved in the hypercoagulable state of tumors and promotes malignant tumors through coagulation-dependent or non-coagulation-dependent pathways. TF-dependent signaling is also involved in divergent cancer progression. Thus, TF-targeted therapeutics could have broad clinical applicability for the treatment of tumors.

Platelet-derived growth factors (PDGFs) and PDGF receptors (PDGFRs) are expressed in a variety of tumors. Activation of the PDGF/PDGFR signaling pathway is associated with cancer proliferation, metastasis, invasion, and angiogenesis through modulating multiple downstream pathways, including phosphatidylinositol 3 kinase/protein kinase B pathway and mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. Therefore, targeting PDGF/PDGFR signaling pathway has been demonstrated to be an effective strategy for cancer therapy, and accordingly, some great progress has been made in this field in the past few decades. This review will focus on the PDGF isoforms and their binding with the related PDGFRs, the PDGF/PDGFR signaling and regulation, and especially present strategies and inhibitors developed for cancer therapy, and the related clinical benefits and side effects.

In recent years, with the development of nanomaterials, the research of drug delivery systems has become a new field of cancer therapy. Compared with conventional antitumor drugs, drug delivery systems such as drug nanoparticles (NPs) are expected to have more advantages in antineoplastic effects, including easy preparation, high efficiency, low toxicity, especially active tumor-targeting ability. Drug delivery systems are usually composed of delivery carriers, antitumor drugs, and even target molecules. At present, there are few comprehensive reports on a summary of drug delivery systems applied for tumor therapy. This review introduces the preparation, characteristics, and applications of several common delivery carriers and expounds the antitumor mechanism of different antitumor drugs in delivery carriers in detail which provides a more theoretical basis for clinical application of personalized cancer nanomedicine in the future.

Metabolic aberrance is one of the hallmarks of cancer. The metabolic patterns in cancer cells are well reprogrammed to provide building blocks and energy for their sustained growth. During tumor metabolic reprogramming, reactive oxygen species (ROS) are generated and the antioxidant systems are activated. High levels of ROS lead to oxidative damage and even cell death, whereas ROS at low levels act as second messenger to regulate many signaling pathways. Recently, with the revisiting of oxidative stress, it has been found that ROS can directly mediate the redox modifications of proteins, resulting in protein conformational and functional alterations. However, only a very small portion of metabolic enzymes, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and PKM2, etc., has been reported to undergo redox modifications. Whether other metabolic enzymes are regulated by redox modifications and thus exhibit critical functions remain largely unknown. Moreover, the specific spatio-temporal targeting of redox modifications of metabolic enzymes, as well as overcoming the existed redox and metabolic adaptation, are key points to be solved. Here, we will review the reported redox modification patterns of metabolic enzymes, the involved regulatory mechanisms and their roles in tumorigenesis and tumor progress. In addition, we will discuss the future therapeutic strategies targeting redox modifications of metabolic enzymes for tumor treatment.

BACKGROUND: Currently, the most important challenge in the development of therapeutics and actives is their poor aqueous solubility and bioavailability.
OBJECTIVE: The low aqueous solubility, poor pharmacokinetic properties, and bioavailability associated with novel actives manifest in numerous challenges in the formulation of conventional dosage forms like tablets, capsules, suspensions, emulsions, etc. Nanosponges are a novel class of drug delivery system capable of encapsulating or entrapping both lipophilic and hydrophilic drugs. Target-specific drug delivery and controlled drug release are the advantages offered by nanosponges which make them a promising anti-tumor drug delivery system.
METHODS: Nanosponges are colloidal structures comprising solid nanoparticles with cavities and meshlike structures for encapsulation of wide varieties of substances like antineoplastic agents, proteins and peptides, volatile oils, genetic material, etc. The methods of preparation of β-cyclodextrin-based nanosponges include solvent evaporation method, emulsion solvent evaporation method, ultrasound-assisted synthesis, hyper cross-linked cyclodextrin and interfacial phenomenon method. A large variety of nanosponges- based formulations are available in the market and some formulations of prostavastin, brexin, glymesason, mena-gargle, etc. are under clinical trials.
RESULTS: Nanosponges possess potential applications in target site-specific drug delivery to liver, spleen, and lungs. Due to the surface functionalization, nanosponges show broad applications in water purification, protein delivery, chemical sensors, detection of explosives, agriculture, etc. In the near future, nanosponges-based products will capture a huge market for commercialization due to their improved properties and advantages.
CONCLUSIONS: This review provides an account of the patents related to nanosponges (2006-2018) and covers the broad applications of β-cyclodextrin-based nanosponges, their roles in vaccine delivery, cancer therapy, fire engineering, water purification, etc.