Breast cancer, as a malignant tumor with easy metastasis and poor prognosis, threatens the health of women around the world. Increasing studies have shown that the Bcl-2 family of apoptosis-related proteins is often expressed abnormally in breast cancer. The Bcl-2 homology 3 (BH3) mimetic peptide can bind and neutralize Bcl-2, preventing its binding to the apoptosis "effector" proteins Bak and Bax, thereby promoting the apoptosis process. However, there is a lack of effective intracellular delivery system for BH3 to exert its biological activity. Therefore, this study utilized an activatable supercharged polypeptide (ASCP) tumor-targeted delivery platform based on pH and protease response to achieve the targeted release of BH3 at the tumor site. Ultimately, intracellular delivery of BH3 was achieved and induced apoptosis of breast tumor cells, preventing the development of breast cancer.

Protein S-nitrosylation (SNO), emerging as an important posttranslational modification, involves covalent addition of nitric oxide (NO) to the sulfur atom of cysteine in proteins. Accumulated evidence suggests that protein SNO plays crucial roles in pathophysiological mechanisms in cancer, which is attracting great attention. However, there are still controversies about whether S-nitrosylated proteins act as oncogenic proteins or tumor suppressors in cancer. In this review, we provide an overview of the early and latest evidence regarding the underlying mechanism and dual roles of SNO in cancer, in an effort to clarify its contribution in tumor progression. It has been well established that S-nitrosylated proteins restrain tumor progression in several types of cancer, while they have exhibited activities in promoting cell proliferation and inhibiting apoptosis in some other kinds of cancer. Interestingly, emerging evidence also has highlighted both its anti-cancer and pro-tumorigenic roles in several other cancer diseases. Finally, current limitations and future research prospects are presented. The overview of targeting SNO in cancer will provide new opportunities for drug development through in-depth exploration of SNO-mediated signaling pathways.

Peripheral nerve injury is a serious and disabling disease prevalent in the world. It caused by trauma is often accompanied with soft tissue injuries, fractures, infections, etc., and can cause permanent damage. The treatment methods of peripheral nerve injury mainly include traditional microsurgical repair, neurotrophic drug treatment, as well as cuttingedge nerve conduit treatment, nerve stimulation, cell therapy, etc. However, more than 30% of patients with peripheral nerve injury still have poor recovery, including partial loss or complete loss of motor and/or sensory function, muscle atrophy，chronic pain and severe disability, among can lead to permanent disease. Phenolic compounds are secondary metabolites which is the most abundant in plants, consisting of an aromatic ring and one or more hydroxyl substituents, the main groups including flavonoids, phenolic acids, tannins, stilbene and lignans. A lot of studies have shown that natural phenolic compounds have various properties, such as antioxidant, anti-infective, anticancer, anti-inflammatory, etc., and have broad applications in the prevention of heart disease, cancer, diabetes, oxidative stress-related diseases, and neuroprotection prospect. This review discusses the potential applications and molecular mechanisms of natural phenolic compounds its polymer derivatives in the treatment of peripheral nerve injury.

Nanozyme with biomimetic enzyme activity has the advantages of good catalytic performance, high stability, and is not easily affected by temperature. However, the application of tumor microenvironment (TME) in the tumor is limited due to its low catalytic activity. Herein, a multifunctional nanozyme based on CuCoP with multivalent metal ions (Cu+/Cu2+ and Co2+/ Co3+) provides an innovative strategy for constructing acid-responsive cancer therapy. CuCoP has excellent photothermal properties (photothermal conversion efficiency of 66.9%) as well as glutathione (GSH) peroxidase activity and high photo-enhanced peroxidase-like (POD) enzyme activity in weak acid TME. CuCoP can consume the overexpressed GSH, thus alleviating the antioxidant capacity of the tumor, and reduces Cu2+/ Co3+ to Cu+/ Co 2+. Subsequently, the generated Cu+/Co2+ will react with endogenous H2O2 to generate cytotoxic hydroxyl radical (•OH), which have high catalytic efficiency in weakly acidic TME. Crucially, the synergistic effect of PTT and the cascade reaction of bimetallic atoms with GSH and H2O2 can effectively reduce antioxidant capacity, inhibit tumors and trigger effective immune cell death (ICD) process, which caused a strong immune response and inhibit tumor recurrence and metastasis. As a novel bimetallic sulfide nanoenzyme triggered by TME, CuCoP has great research value in cancer therapy.

The requirement of having multiple nanocarriers (NCs) and active agents for improved therapy, imaging, and controlled release of medications efficiently in one platform has made the creation of therapeutics and theragnostic nanodrug delivery systems a difficult task for present researchers. Multiple drug resistance (MDR), a high clearance rate, severe side effects, undesirable drug distribution to the specific site of liver cancer, and a low concentration of medication that reaches liver cancer cells are just a few of the drawbacks of traditional liver cancer chemotherapy. As a result, new techniques and NCs must be developed to transport the medication molecules targeted to the malignant hepatocytes in an acceptable number and duration inside the therapeutic window. Because of the great efficacy of drug loading or drug encapsulation efficiency, high cellular uptake, high drug release, and minimal adverse effects, therapeutics and theragnostic systems have benefits over conventional chemotherapy. These NCs have a high drug accumulation rate in tumours while causing minimal toxicity in healthy tissues. This study focuses on current research on NC-based therapies and theragnostic drug delivery systems, omitting nanotechnology's negative consequences in the field of drug delivery systems. Clinical advancements of theragnostic NCs for liver cancer, on the other hand, are not covered in this article. Only the most current breakthroughs in NC-based drug delivery systems for liver cancer therapy and diagnosis are discussed in this study. This review will not go over the detrimental effects of individual NCs in the medication delivery system.

Adenosine alterations to RNA, which are largely determined by RNA modification writers (RMWs), are critical for cancer growth and progression. These RMWs can catalyze different types of adenosine modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), alternative polyadenylation (APA), and adenosine-to-inosine (A-to-I) RNA editing. These modifications have profound effects on gene expression and function, such as immune response, cell development. Despite this, the clinical effects of RMW interactive genes on these cancers remain largely unclear. A comprehensive analysis of the clinical impact of these epigenetic regulators in pan-cancer requires further comprehensive exploration. Here, we systematically profiled the molecular and clinical characteristics of 26 RMWs across 33 cancer types using multi-omics datasets and validated the expression level of some RMWs in various cancer lines. Our findings indicated that a majority of RMWs exhibited high expression in diverse cancer types, and this expression was found to be significantly associated with poor patient outcomes. In the genetic alterations, the amplification and mutation of RMWs were the dominant alteration events. Consequently, the RNA Modification Writer Score (RMW score) was established as a means to assess the risk of RMWs in pan-cancer. We found that 27 of 33 cancers had significantly higher scores compared with normal tissues, and it was significantly correlated with prognosis. We also evaluated their impact on the tumor microenvironment and the response to immunotherapy and targeted therapy. These findings verified the important role of RMWs in different aspects of cancer biology, and provided biomarkers and personalized therapeutic targets for cancer.