Toxic Side Effects Research Articles

Efficacy and safety of anlotinib as maintenance therapy in patients with advanced non-small cell lung cancer achieving SD post first-line chemotherapy combined with immunotherapy.

Advanced non-small cell lung cancer (NSCLC) remains a significant clinical challenge, particularly in patients who exhibit stable disease (SD) following first-line chemotherapy combined with immunotherapy. This study aims to evaluate the efficacy and safety of Anlotinib, a novel multitarget tyrosine kinase inhibitor, as maintenance therapy in this patient cohort. This retrospective, single-center study enrolled patients with advanced NSCLC who showed SD after receiving a combination of first-line chemo-immunotherapy for 4 cycles, then add anlotinib to subsequent standard maintenance therapy, continuing treatment until disease progression or the occurrence of intolerable toxic side effects. The primary endpoint was progression-free survival (P FS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety profile. A total of 52 patients were enrolled, the median P FS and OS was 5.0m and 10.0m, respectively. The ORR and DCR was 28.85% and 67.31%. subgroup analysis indicated that its efficacy correlate with certain Adverse Effects (AEs, such as hypertension, proteinuria, and hand-foot syndrome). Further mechanistic analysis suggests that this regimen may likely reduce immune suppression by depleting Tregs, thereby further activating the immune system to exert synergistic anti-tumor effects. Besides promising efficacy, the toxicity can be tolerated. Anlotinib demonstrates promising efficacy as a maintenance therapy in patients with advanced NSCLC who have achieved SD following first-line chemotherapy combined with immunotherapy. The manageable safety profile and the observed extension in P FS and OS suggest that Anlotinib could be a valuable therapeutic option for this challenging patient population. Further large-scale randomized controlled trials are warranted to confirm these findings and to optimize patient selection and management strategies.

A pH-Responsive Drug-Delivery System Based on Apatinib-Loaded Metal-Organic Frameworks for Ferroptosis-Targeted Synergistic Anti-Tumor Therapy.

The efficacy of systemic therapy for hepatocellular carcinoma (HCC) is limited mainly by the complex tumor defense mechanism and the severe toxic side-effects of drugs. The efficacy of apatinib (Apa), a key liver cancer treatment, is unsatisfactory due to inadequate targeting and is accompanied by notable side-effects. Leveraging nanomaterials to enhance its targeting represents a crucial strategy for improving the effectiveness of liver cancer therapy. A metal polyphenol network-coated apatinib-loaded metal-organic framework-based multifunctional drug-delivery system (MIL-100@Apa@MPN) was prepared by using metal-organic frameworks (MOFs) as carriers. The nanoparticles (NPs) were subsequently characterized using techniques such as X-ray diffraction (XRD), transmission electron microscopy (TEM), zeta potential measurements, and particle size analysis. In vitro experiments were conducted to observe the drug release kinetics and cytotoxic effects of MIL-100@Apa@MPN on HepG2 cells. The in vivo anti-tumor efficacy of MIL-100@Apa@MPN was evaluated using the H22 tumor-bearing mouse model. The formulated MIL-100@Apa@MPN demonstrates remarkable thermal stability and possesses a uniform structure, with measured drug-loading (DL) and encapsulation efficiency (EE) rates of 28.33% and 85.01%, respectively. In vitro studies demonstrated that HepG2 cells efficiently uptake coumarin-6-loaded NPs, and a significant increase in cumulative drug release was observed under lower pH conditions (pH 5.0), leading to the release of approximately 73.72% of Apa. In HepG2 cells, MIL-100@Apa@MPN exhibited more significant antiproliferative activity compared to free Apa. In vivo, MIL-100@Apa@MPN significantly inhibited tumor growth, attenuated side-effects, and enhanced therapeutic effects in H22 tumor-bearing mice compared to other groups. We have successfully constructed a MOF delivery system with excellent safety, sustained-release capability, pH-targeting, and improved anti-tumor efficacy, highlighting its potential as a therapeutic approach for the treatment of HCC.

Effective synthesis of fluorescent carbon dots and their application in controllable detection of deferasirox

As an iron chelation therapy, deferasirox (DEF) is commonly used as the primary treatment drug to prevent intracellular iron overload in patients with thalassemia who require long-term and large blood transfusions. However, due to the toxic side effects of long-term use, building a convenient and sensitive DEF detection method remains an important task. This study developed a simple and effective fluorescence detection strategy for DEF based on the coordination effect of DEF and Cu2+ (DEF-Cu). The high quantum yield N-doped blue emission carbon dots (CDs) synthesized by a simple one-step hydrothermal method were applied as the fluorescent probe. The DEF-Cu exhibited a new absorption peak centered at 334 nm, overlapping with the absorption wavelength of CDs, resulting in an internal filtration effect (IFE) for quenching the fluorescence of CDs. The quenching degrees of CDs caused by DEF-Cu showed a good linear relationship in the range of 0.5–20 μg/mL, with a detection limit (LOD) as low as 0.12 μg/mL. The accurate detections of DEF in dispersible tablets and plasma were also achieved. This strategy not only enriched the understanding of the properties of target drugs but also provided valuable insights for designing CDs with specific luminescent properties and applying them to distinctive methods for drug analysis.

Targeted counteracting of overactive macrophages by melittin stable-loaded solid lipid nanoparticles alleviates cytokine storm and acute inflammatory injury

The continuous activation of macrophages play a critical role in the pathogenesis of cytokine storm (CS). Considering that CS results from the participation of multiple cytokines, the therapeutic effect of a single cytokine or its receptor-targeted blockade therapy remains uncertain. Melittin, which can systematically suppress the overexpression of proinflammatory mediators via inhibiting the mitogen-activated protein kinase and nuclear factor kappa-B pathways in activated macrophages, shows great potential in alleviating CS and acute inflammatory injury (AII). However, its clinical application is limited by its hemolytic activity, non-specific cytotoxicity and lack of targeting. In this study, a folic acid-modified and melittin stable-loaded solid lipid nanoparticle (Fa-MpG@LNP) with a core–shell structure was developed for CS control via targeted inhibition of the overproduction of proinflammatory mediators in activated macrophages with specific expression of folate receptor-β. The resultant Fa-MpG@LNP showed ideal physicochemical properties and stability, low hemolytic activity and non-specific cytotoxicity, and it can specifically bind to lipopolysaccharide (LPS)-stimulated macrophages and effectively reduce the elevated levels of proinflammatory mediators. After intravenous administration, the Fa-MpG@LNP accumulated at inflamed tissue and significantly downregulate the overproduction of proinflammatory cytokines in tissue-infiltrated macrophages, resulting in a significant decrease of cytokine concentration in inflamed tissue and serum in LPS-induced acute pneumonia mice, and finally alleviate AII with undetectable toxic side effects. These results indicate the clinical application potential of Fa-MpG@LNP in alleviating CS and its related symptoms.

Cognitive Impairment from Breast Cancer Chemotherapy in the Perspective of Traditional Chinese Medicine

In recent years, the incidence of breast cancer has been on the rise globally and in China. The conventional treatment methods for breast cancer include surgery, radiotherapy, chemotherapy, endocrine therapy, targeted therapy, traditional Chinese medicine, and other biological immunotherapy. In the treatment of breast cancer, the status of chemotherapy drugs is unshakable, and the related toxic side effects have gradually attracted people's attention. Doxorubicin is an anthracycline drug, which is the cornerstone drug for adjuvant chemotherapy for breast cancer. It exerts anti-tumor effects by inserting DNA and inhibiting topoisomerase II, but it can also cause severe neurotoxicity by crossing the blood-brain barrier, clinically manifested as memory and executive function decline, etc., which has a huge impact on the patient's work and life. With the development of modern medicine, the advantages of traditional Chinese medicine in preventing and treating adverse reactions related to breast cancer and improving patients' quality of life are increasingly being recognized. Traditional Chinese medicine classifies chemotherapy-induced cognitive impairment into related diseases such as "dementia", "brain marrow depletion", and "forgetfulness" based on its main clinical symptoms, and achieves the therapeutic effect of improving chemotherapy-induced cognitive impairment through clinical differentiation and coordinating relevant therapies, providing a scientific basis for the treatment of adverse reactions related to malignant tumors by traditional Chinese medicine in radiotherapy and chemotherapy.

Unlocking lysosomal acidity to activate membranolytic module for accurately cancer theranostics

Chemotherapy drug efflux, toxic side effects, and low efficacy against drug-resistant cells have plagued safe and efficient cancer theranostics. However, the materials or methods that resolve these defects all-in-one are scarce. Here, a new cancer theranostics strategy is proposed by utilizing changes in lysosomal acidity in cancer cells to activate the membranolytic model to overcome these obstacles together. Therefore, a simple fluorescent anthracene derivative Lyso-Mito is developed, which has a perfect pKa (4.62) value that falls between the pH of lysosomes in cancer and normal cells. Lyso-Mito itself can precisely target and convert the pH perturbation of lysosomes in cancer cells to fluorescent response and membranolytic module activity to accomplish the low drug efflux, weak toxic side effects, and low drug-resistant cancer diagnosis and treatment without linking other functional units or any additional assistance. Hereby, a new cancer theranostics strategy of integrating organelle microenvironment and the membranolytic model is realized.

Magnetic stirring with iron oxide nanospinners accretes neurotoxic Aβ42 oligomers into phagocytic clearable plaques for Alzheimer's disease treatment

An increasing number of medications have been explored to treat the progressive and irreversible Alzheimer's disease (AD) that stands as the predominant form of dementia among neurodegenerative ailments. However, assertions about toxic side effects of these drugs are a significant hurdle to overcome, calling for drug-free nanotherapeutics. Herein, a new therapeutic strategy devoid of conventional drugs or other cytotoxic species was developed. The constructed superparamagnetic iron oxide nanoparticles (SPIONs) nanospinners can accrete neurotoxic β-amyloid 42 oligomers (oAβ42) into aggregated magnetic plaques (mpAβ) by mechanical rotating force via remote interaction between nanoparticles and the applied magnetic field. While the cellular uptake of mpAβ attained from the magnetic stirring treatment by neuronal cells is severely limited, the facile phagocytic uptake of mpAβ by microglial cells leads to the polarization of the brain macrophages to M2 phenotype and thus the increased anti-inflammatory responses to the treatment. The SPION stirring treatment protects the AD mice from memory deterioration and maintain cognitive ability as evidenced from both nesting and Barnes maze tests. The examination of the oAβ42 injected brain tissues with the stirring treatment showed significant amelioration of functional impairment of neurons, microglia, astrocytes and oligodendrocytes alongside no obvious tissue damage caused by stirring meanwhile complete degradation of SPION was observed at day 7 after the treatment. The in vitro and animal data of this work strongly corroborate that this new modality of undruggable stirring treatment with SPIONs provides a new feasible strategy for developing novel AD treatments.

Design of Novel HIV-1 Protease Inhibitors with Favorable Oral Properties using a Molecular Modelling Approach

Acquired immunodeficiency syndrome (AIDS) is a chronic and potentially fatal transmissible disease caused by the Human Immunodeficiency Virus (HIV). Since its discovery in 1981, an estimated 85 million cases and 40 million AIDS related deaths have occurred worldwide. Among the two types of HIV, HIV-1 accounts for over 90% of reported cases. Throughout the years, multiple drugs have been approved for the treatment of AIDS. However, these drugs face many drawbacks such as toxic side effects, non-optimal pharmacodynamic profile and drug resistance due to virus mutation. This study aims to design novel potent HIV-1 protease inhibitors that overcome these drawbacks through molecular modelling methods. Pubchem database was screened for potential lead compounds. Results were filtered through two phases of ADMET and docking studies. Finally, the chosen lead compound was optimized through fragment replacement to obtain the novel inhibitors.

Fermentation: improvement of pharmacological effects and applications of botanical drugs.

Fermentation is an important concoction technique for botanical drugs. Fermentation transforms and enhances the active ingredients of botanical drugs through specific microbiological processes, ultimately affecting their pharmacological effects. This review explores the use of fermented botanical drugs in areas such as anti-tumor, hypolipidemic, antioxidant, antimicrobial, cosmetology, and intestinal flora regulation. It elucidates the potential pharmacological mechanisms and discusses the benefits of fermentation technology for botanical drugs, including reducing toxic side effects, enhancing drug efficacy, and creating new active ingredients. This article also discussesdelves into the common strains and factors influencing the fermentation process, which are crucial for the successful transformation and enhancement of these drugs. Taken together, this study aimed to provide a reference point for further research and wider applications of botanical drug fermentation technology.

Unveiling gut microbiota's role: Bidirectional regulation of drug transport for improved safety.

Drug safety is a paramount concern in the field of drug development, with researchers increasingly focusing on the bidirectional regulation of gut microbiota in this context. The gut microbiota plays a crucial role in maintaining drug safety. It can influence drug transport processes in the body through various mechanisms, thereby modulating their efficacy and toxicity. The main mechanisms include: (1) The gut microbiota directly interacts with drugs, altering their chemical structure to reduce toxicity and enhance efficacy, thereby impacting drug transport mechanisms, drugs can also change the structure and abundance of gut bacteria; (2) bidirectional regulation of intestinal barrier permeability by gut microbiota, promoting the absorption of nontoxic drugs and inhibiting the absorption of toxic components; (3) bidirectional regulation of the expression and activity of transport proteins by gut microbiota, selectively promoting the absorption of effective components or inhibiting the absorption of toxic components. This bidirectional regulatory role enables the gut microbiota to play a key role in maintaining drug balance in the body and reducing adverse reactions. Understanding these regulatory mechanisms sheds light on novel approaches to minimize toxic side effects, enhance drug efficacy, and ultimately improve drug safety. This review systematically examines the bidirectional regulation of gut microbiota in drug transportation from the aforementioned aspects, emphasizing their significance in ensuring drug safety. Furthermore, it offers a prospective outlook from the standpoint of enhancing therapeutic efficacy and reducing drug toxicity, underscoring the importance of further exploration in this research domain. It aims to provide more effective strategies for drug development and treatment.

Novel Diacyl-hydrazide Compounds as Potential Therapeutics for Visceral Leishmaniasis.

Visceral leishmaniasis is a neglected tropical disease with the highest mortality among different forms of leishmaniasis manifestation in humans. The disease is caused by the parasitic protists Leishmania donovani and Leishmania infantum, and treatments remain unsuitable due to high costs, complicated administration, lack of efficacy, variable patient susceptibility, toxic side effects, and rising parasitic resistance. Herein, we report a structure-activity relationship (SAR) exploration of the diacyl-hydrazide scaffold identified to have antiparasitic activity from a high-throughput screen against L. donovani, Trypanosoma cruzi, and Trypanosoma brucei. This SAR study revealed new structural insights into this scaffold related to bioactivity resulting in a new series of lead compounds with nanomolar activity against L. donovani and no toxicity against human THP-1 macrophages. These optimized diacyl-hydrazide compounds set the stage for future drug development and hold promise for a new treatment avenue for visceral leishmaniasis.

A negatively charged polyethersulfone nanofiltration membrane enriched with Ag-functionalized titanium silicon carbide for the removal of organic pollutants from water

Developing high-performance nanofiltration membranes for treating wastewater contaminated with organic pollutants requires special attention. The toxic nature and side effects of organic pollutants, such as dyes and antibiotics, make them hazardous. Therefore, wastewater containing organic pollutants must be treated properly before entering water environments. Herein, we synthesized the Ti3SiC2 MAX phase via the reactive sintering technique. To make the Ti3SiC2 more hydrophilic and compatible with the polyethersulfone (PES) membrane, its surface was modified in one step with Ag NPs/polyvinyl alcohol (Ag-MAX). Different quantities (0–1 wt%) of Ag-MAX filler were embedded into the PES membrane via the phase inversion process. The presence of 0.75 wt% Ag-MAX filler enhanced hydrophilicity, porosity, surface roughness, pore size, and negative charge of PES membrane, which are beneficial for permeance and antifouling features of Ag-MAX mixed matrix membranes (MMMs). The optimized membrane containing 0.75 wt% of Ag-MAX demonstrated the uppermost pure water flux of 72.5 L/m2 h with a flux recovery ratio of 82.8 %. The optimized membrane showed rejection efficiency of 99.4, 99.6, and 99.7 % for Direct Black 38, Acid Blue 113, and Disperse Red 153 dye solutions, along with a satisfactory rejection of 70.7, 65.9, and 58.5 % for Basic Violet 1, Alizarin Red S, and Ceftriaxone solutions, respectively. Furthermore, the effects of various pH values, various salt types, and cyclic filtration experiments on the separation performance of 0.75 wt% Ag-MAX MMM were investigated. The rejection efficiency of 0.75 wt% Ag-MAX MMM toward Acid Blue 113 is almost constant and higher than 98.5 % in different conditions, demonstrating that the Ag-MAX MMM could be a suitable candidate for the treatment of wastewater contaminated with organic pollutants.

MMFSyn: A Multimodal Deep Learning Model for Predicting Anticancer Synergistic Drug Combination Effect.

Combination therapy aims to synergistically enhance efficacy or reduce toxic side effects and has widely been used in clinical practice. However, with the rapid increase in the types of drug combinations, identifying the synergistic relationships between drugs remains a highly challenging task. This paper proposes a novel deep learning model MMFSyn based on multimodal drug data combined with cell line features. Firstly, to ensure the full expression of drug molecular features, multiple modalities of drugs, including Morgan fingerprints, atom sequences, molecular diagrams, and atomic point cloud data, are extracted using SMILES. Secondly, for different modal data, a Bi-LSTM, gMLP, multi-head attention mechanism, and multi-scale GCNs are comprehensively applied to extract the drug feature. Then, it selects appropriate omics features from gene expression and mutation omics data of cancer cell lines to construct cancer cell line features. Finally, these features are combined to predict the synergistic anti-cancer drug combination effect. The experimental results verify that MMFSyn has significant advantages in performance compared to other popular methods, with a root mean square error of 13.33 and a Pearson correlation coefficient of 0.81, which indicates that MMFSyn can better capture the complex relationship between multimodal drug combinations and omics data, thereby improving the synergistic drug combination prediction.

Red Blood Cell Membrane Spontaneously Coated Nanoprodrug Based on Phosphatidylserine for Antiatherosclerosis Applications.

Atherosclerosis (AS) is characterized by the accumulation of lipids within the walls of coronary arteries, leading to arterial narrowing and hardening. It serves as the primary etiology and pathological basis for cardiovascular diseases affecting the heart and brain. However, conventional pharmacotherapy is constrained by inadequate drug delivery and pronounced toxic side effects. Moreover, the inefficacy of nanomedicine delivery systems in controlling disease progression may be attributed to nonspecific clearance by the mononuclear phagocyte system. Thus, a biomimetic platform spontaneously enveloped by red blood cell membrane is exploited for anti-atherosclerosis applications, offering favorable biocompatibility. The CLIKKPF polypeptide is introduced to develop red blood cell membrane spontaneously encapsulated nanotherapeutics only through simple coincubation. Given the functional modifications, RBC@P-LVTNPs is beneficial to facilitate the target drug delivery to the atherosclerotic lesion, responding precisely to the pathological ROS accumulation, thereby accelerating the on-demand drug release. Both in vivo and in vitro results also confirm the significant therapeutic efficacy and favorable biocompatibility of the biomimetic nanomedicine delivery system, thus providing a promising candidate for nanotherapeutics against AS.

The Therapeutic Mechanisms of Honey in Mitigating Toxicity from Anticancer Chemotherapy Toxicity: A Review.

Within the domain of conventional oncochemotherapeutics, anticancer chemotherapy (AC) has emerged as a potent strategy for the treatment of cancers. AC is the mainstay strategy for solid and non-solid cancer treatment. Its mechanistic action targets the blockage of DNA transcription and the dysregulation of cell cycle machinery in cancer cells, leading to the activation of death pathways. However, the attendant side effect of toxicity inflicted by AC on healthy tissues presents a formidable challenge. The crucial culprit in the AC side effect of toxicity is unknown, although oxidative stress, mitochondrial impairment, inflammatory cascades, autophagy dysregulation, apoptosis, and certain aberrant signaling have been implicated. Honey is a natural bee product with significant health benefits and pharmacological properties. Interestingly, the literature reports that honey may proffer a protection mechanism for delicate tissue/organs against the side effect of toxicity from AC. Thus, this review delves into the prospective role of honey as an alleviator of the AC side effect of toxicity; it provides an elucidation of the mechanisms of AC toxicity and honey's molecular mechanisms of mitigation. The review endeavors to unravel the specific molecular cascades by which honey orchestrates its mitigating effects, with the overarching objective of refining its application as an adjuvant natural product. Honey supplementation prevents AC toxicity via the inhibition of oxidative stress, NF-κB-mediated inflammation, and caspase-dependent apoptosis cascades. Although there is a need for increased mechanistic studies, honey is a natural product that could mitigate the various toxicities induced by AC.

Methotrexate-Loaded Chitosan Oligosaccharide-ES2 for Targeted Cancer Therapy.

Cancer presents a significant health threat, necessitating the development of more precise, efficient, and less damaging treatment approaches. To address this challenge, we employed the 1-ethyl-(3-dimethyl aminopropyl) carbodiimide/N-hydroxy succinimide (EDC/NHS) catalytic system and utilized quaternized chitosan oligosaccharide (HTCOSC) as a drug carrier to construct a nanoparticle delivery system termed HTCOSC-cRGD-ES2-MTX (CREM). This system specifically targets integrin αvβ3 on tumor cell surfaces and enables simultaneous loading of the antiangiogenic agent ES2 (IVRRADRAAVP) and the chemotherapy drug methotrexate (MTX). Due to its amphiphilic properties, CREM self-assembles into nanoparticles in aqueous solution, exhibiting an average diameter of 179.47 nm. Comparative studies demonstrated that CREM, in contrast to free ES2 and MTX-free nanoparticles (CRE), significantly suppressed the proliferation of EAhy926 endothelial cells and B16 melanoma cells in vitro, resulting in inhibition rates of 71.18 and 82.25%, respectively. Furthermore, CREM exhibited a hemolysis rate below 2%, indicating excellent in vitro antiangiogenic and antitumor activity as well as favorable blood compatibility. Additionally, both CRE and CREM demonstrated favorable tumor targeting capabilities through the specific binding action of cyclic RGD (cRGD) to integrin αvβ3. Further in vivo investigations revealed that CREM induced apoptosis in tumor cells via the mitochondrial apoptotic pathway and reduced the expression of angiogenic factors such as vascular endothelial growth factor (VEGF), thereby inhibiting tumor angiogenesis. This potent antitumor effect was evident through a tumor suppression rate of 80.19%. Importantly, histopathological staining (HE staining) demonstrated the absence of significant toxic side effects of CREM on various organs compared to MTX. In conclusion, the CREM nano drug delivery system synergistically enhances the therapeutic efficacy of antiangiogenic drugs and chemotherapeutic agents, thus offering a novel targeted approach for cancer treatment.

PF127/bleomycin hydrogel promotes subcutaneous extracellular matrix remodeling and fibrosis to construct personalized flaps through the TGFβ-Col signaling pathway

Background Skin flap transplantation is used to effectively reconstruct defects of the hand and foot skin and soft tissues. We here investigated the effect of the PF127/bleomycin (BLM) hydrogel on the extracellular matrix (ECM) remodeling of skin flaps and the underlying mechanism, thereby providing a new reference point for personalized flap modification and overcoming abrasion resistance- and stability-associated difficulties. Methods The appropriate PF127/BLM concentration was selected based on the gelation time and drug release curve. Migration assays, scratch assays, and live/dead staining were conducted to verify the effect of PF127/BLM on human skin fibroblasts (HSFs). The effects of PF127/BLM on the ECM were assessed through hematoxylin and eosin and Masson staining. Additionally, we examined the expression of ECM remodeling-related genes and proteins involved in their associated signaling pathway. Finally, the effects of PF127/BLM on organ fibrosis and toxicity to liver and kidney functions were assessed in mice. Results A 25% PF127/BLM hydrogel was selected as the study concentration. PF127/BLM augmented HSF chemotaxis and proliferation. Furthermore, PF127/BLM promoted subcutaneous ECM remodeling and fibrosis, increased the flap dermis thickness, and reduced the toxic side effects of BLM on liver/lung fibrosis and liver/kidney function. Additional studies confirmed that the PF127/BLM-mediated regulation of ECM remodeling in skin flaps was associated with TGFβ-Col signaling pathway activation. Conclusion The PF127/BLM hydrogel promoted subcutaneous ECM remodeling and fibrosis, which aided the construction of personalized flaps through the TGFβ-Col signaling pathway, with decreased hepatic, pulmonary, and renal toxicities.

In vivo fluorescence flow cytometry reveals that the nanoparticle tumor vaccine OVA@HA-PEI effectively clears circulating tumor cells

Tumor vaccine therapy offers significant advantages over conventional treatments, including reduced toxic side effects. However, it currently functions primarily as an adjuvant treatment modality in clinical oncology due to limitations in tumor antigen selection and delivery methods. Tumor vaccines often fail to elicit a sufficiently robust immune response against progressive tumors, thereby limiting their clinical efficacy. In this study, we developed a nanoparticle-based tumor vaccine, OVA@HA-PEI, utilizing ovalbumin (OVA) as the presenting antigen and hyaluronic acid (HA) and polyethyleneimine (PEI) as adjuvants and carriers. This formulation significantly enhanced the proliferation of immune cells and cytokines, such as CD3, CD8, interferon-[Formula: see text], and tumor necrosis factor-[Formula: see text], in vivo, effectively activating an immune response against B16–F10 tumors. In vivo fluorescence flow cytometry (IVFC) has already become an effective method for monitoring circulating tumor cells (CTCs) due to its direct, noninvasive, and long-term detection capabilities. Our study utilized a laboratory-constructed IVFC system to monitor the immune processes induced by the OVA@HA-PEI tumor vaccine and an anti-programmed death-1 (PD-1) antibody. The results demonstrated that the combined treatment of OVA@HA-PEI and anti-PD-1 antibody significantly improved the survival time of mice compared to anti-PD-1 antibody treatment alone. Additionally, this combination therapy substantially reduced the number of CTCs in vivo, increased the clearance rate of CTCs by the immune system, and slowed tumor progression. These findings greatly enhance the clinical application prospects of IVFC and tumor vaccines.

Gypenoside inhibits gastric cancer proliferation by suppressing glycolysis via the Hippo pathway

Gastric cancer (GC) remains a global disease with a high mortality rate, the lack of effective treatments and the high toxicity of side effects are primary causes for its poor prognosis. Hence, urgent efforts are needed to find safe and effective therapeutic strategies. Gypenoside (Gyp) is a widely used natural product that regulates blood glucose to improve disease progression with few toxic side effects. Given the crucial role of abnormal glycometabolism in driving tumor malignancy, it is important to explore the association between Gyp and glycometabolism in GC and understand the mechanism of action by which Gyp influences glycometabolism. In this study, we demonstrated that Gyp suppresses GC proliferation and migration both in vitro and in vivo. We identified that Gyp suppresses the malignant progression of GC by inhibiting glycolysis using network pharmacology and metabolomics. Transcriptome analysis revealed that the Hippo pathway is a key regulator of glycolysis by Gyp in GC. Furthermore, Gyp induced upregulation of LATS1/2 proteins, leading to increased YAP phosphorylation and decreased TAZ protein expression. The YAP agonist XMU-MP-1 rescued the inhibitory effect of Gyp on GC proliferation by reversing glycolysis. These findings confirmed that Gyp inhibits GC proliferation by targeting glycolysis through the Hippo pathway. Our study examined the role of Gyp in the malignant progression of GC, explored its therapeutic prospects, elucidated a mechanism by which Gyp suppresses GC proliferation through interference with the glycolytic process, thus providing a potential novel therapeutic strategy for GC patients.

Preparation of double-loaded bitter ginseng derivative B21–DOX liposomes co-modified with SP94 and BR2 ligand and its in vitro anti-hepatocarcinogenic effect

Aim To construct a novel liposomal drug delivery system co-modified with SP94 and BR2 ligands, encapsulating both the bitter ginseng derivative B21 and doxorubicin (DOX), to achieve superior anti-tumour efficacy and reduced toxic side effects. Methods Liposomes were prepared using an organic phase reaction method, with B21 encapsulated in the lipid phase and DOX in the aqueous phase. The liposomes were further modified with SP94 and BR2 peptides. The characterisations, cytotoxicity, and in vitro targeting effects were assessed through various methods including ultraviolet spectrophotometry, high-performance liquid chromatography, nano-size analysis, ultrafiltration centrifugation, dialysis, transmission electron microscopy, flow cytometry, Methylthiazolyldiphenyl-tetrazolium bromide assay, confocal laser scanning microscopy, transwell assay, and tumorsphere assay. Results SP94/BR2-B21/DOX-LP liposomes were spherical with an average diameter of 120.87 ± 1.00 nm, a polydispersity index (PDI) of 0.223 ± 0.006, and a surface charge of −23.1 ± 1.27 mV. The encapsulation efficiencies for B21 and DOX were greater than 85% and 97% (mg/mg), respectively. The results indicated that SP94/BR2-B21/DOX-LP exhibited enhanced targeting and cytotoxicity compared to single-ligand modified and unmodified liposomes, with the combined encapsulation of B21 and DOX showing synergistic anti-hepatocarcinogenic effects. Conclusion SP94/BR2-B21/DOX-LP liposomes represent a promising targeted drug delivery system for hepatocellular carcinoma, offering improved membrane penetration, enhanced therapeutic efficacy, and reduced systemic toxicity.