Antitumor Effects Research Articles

STING activation disrupts tumor vasculature to overcome the EPR limitation and increase drug deposition.

The low success rate of cancer nanomedicines has raised debate on the role of the enhanced permeability and retention (EPR) effect on tumor deposition of nanotherapeutics. Here, we report a bifunctional nanoscale coordination polymer (NCP), oxaliplatin (OX)/2',3'-cyclic guanosine monophosphate-adenosine monophosphate (GA), to overcome the EPR limitation through stimulator of interferon genes (STING) activation and enhance chemotherapeutic and STING agonist delivery for tumor eradication. OX/GA encapsulates GA and OX in the NCP to protect GA from enzymatic degradation and improve GA and OX pharmacokinetics. STING activation by OX/GA disrupts tumor vasculatures and increases intratumoral deposition of OX by 4.9-fold over monotherapy OX-NCP. OX/GA demonstrates exceptional antitumor effects with >95% tumor growth inhibition and high cure rates in subcutaneous, orthotopic, spontaneous, and metastatic tumor models. OX/GA induces immunogenic cell death of tumor cells and STING activation of innate immune cells to enhance antigen presentation. NCPs provide an excellent nanoplatform to overcome the EPR limitation for effective cancer therapy.

Nischarin inhibits the epithelial-mesenchymal transition process and angiogenesis in breast cancer cells by inactivating FAK/ERK signaling pathway via EGF like repeats and discoidin domains 3.

Our previous study has demonstrated that Nischarin (NISCH) exerts its antitumor effects in breast cancer (BC) by suppressing cell migration and invasion. This study aims to explore the underlying mechanism through which NISCH functions in BC. The relevance between EGF Like Repeats and Discoidin Domains 3 (EDIL3) mRNA expression and the overall survival of tumor patients was depicted by the Kaplan-Meier curve. The findings revealed that overexpressed NISCH attenuated cell motility and colony-forming capacities of Hs578T cells, yet silenced NISCH in MDA-MB-231 cells led to contrasting results. Western blot (WB) analysis indicated that overexpression of NISCH significantly down-regulated the Vimentin and Slug expression, and inactivated the FAK/ERK signaling pathway. RNA sequencing (RNA-seq) was performed in NISCH-overexpressed Hs578T cells and the control cells to analyze differentially expressed genes (DeGs), and the results showed a significant down-regulation of EDIL3 mRNA level upon overexpression of NISCH. Subsequent functional analyses demonstrated that overexpression of EDIL3 attenuated the inhibitory effect of NISCH on cell migration, invasion, colony formation, and tube formation. In summary, our finding preliminarily revealed that NISCH inhibits the epithelial-mesenchymal transition (EMT) process and angiogenesis in BC cells by down-regulating EDIL3 to inactivate the FAK/ERK signaling pathway, thereby suppressing the progression of BC. Our results hold promise for contributing to the deep understanding of BC pathogenesis and identifying new therapeutic strategies for clinical application.

Dual-Engineered Macrophage-Microbe Encapsulation for Metastasis Immunotherapy.

Lung metastases are the leading cause of death among cancer patients. The challenges of inefficient drug delivery, compounded by a robust immunosuppressive microenvironment, make effective treatment difficult. Here, an innovative dual-engineered macrophage-microbe encapsulation (Du-EMME) therapy is developed that integrates modified macrophages and engineered antitumor bacteria. These engineered macrophages, termed R-GEM cells, are designed to express RGD peptides on extracellular membranes, enhancing their tumor cell binding and intratumor enrichment. R-GEM cells are cocultured with attenuated Salmonella typhimurium VNP20009, producing macrophage-microbe encapsulation (R-GEM/VNP cells). The intracellular bacteria maintain bioactivity for more than 24h, and the bacteria released from R-GEM/VNP cells within the tumor continue to exert bacteria-mediated antitumor effects. This is further supported by macrophage-based chemotaxis and camouflage, which enhance the intratumoral enrichment and biocompatibility of the bacteria. Additionally, R-GEM cells loaded with IFNγ-secreting strains (VNP-IFNγ) form R-GEM/VNP-IFNγ cells. Treatment with these cells effectively halts lung metastatic tumor progression in three mouse models (breast cancer, melanoma, and colorectal cancer). R-GEM/VNP-IFNγ cells vigorously activate the tumor microenvironment, suppressing tumor-promoting M2-type macrophages, MDSCs, and Tregs, and enhancing tumor-antagonizing M1-type macrophages, mature DCs, and Teffs. Du-EMME therapy offers a promising strategy for targeted and enhanced antitumor immunity in treating cancer metastases.

Biological Applications, In Vitro Cytotoxicity, Cellular Uptake, and Apoptotic Pathway Studies Induced by Ternary Cu (II) Complexes Involving Triflupromazine with Biorelevant Ligands.

The novel mixed-ligand complexes derived from the parent antidepressant phenothiazine drug triflupromazine (TFP) were synthesized along with the secondary ligands glycine and histidine. [Cu(TFP)(Gly)Cl]·2H2O (1) and [Cu(TFP)(His)Cl]·2H2O (2) were examined for their in vitro biological properties. Cyclic voltammetry was used to study the binding of both complexes to CT-DNA. The two complexes were examined for antiviral, antiparasite, and anti-inflammatory applications. An in vitro cytotoxicity study on two different cancer cell lines, MCF-7, HepG2, and a normal cell line, HSF, shows promising selective cytotoxicity for cancer cells. An investigation of the cell cycle and apoptosis rates was evaluated by flow cytometry with Annexin V-FITC/Propidium Iodide (PI) staining of the treated cells. Gene expression and western blotting were carried out to determine the expression levels of the pro-apoptotic markers and the anti-apoptotic marker Bcl2. The tested complexes decreased cell viability and triggered apoptosis in human tumor cell lines. Molecular docking was also used to simulate Bcl2 inhibition. Finally, complex (2) has potent antitumor effects on human tumor cells, especially against HepG2 cells, as seen in the cellular drug uptake assay. Consequently, complex (2) may prove useful against cancer, especially liver cancer. For further understanding, it needs to be explored in vivo.

A pH-triggered N-oxide polyzwitterionic nano-drug loaded system for the anti-tumor immunity activation research

Triple negative breast cancer (TNBC) has the characteristics of low immune cell infiltration, high expression of tumor programmed death ligand 1 (PD-L1), and abundant cancer stem cells. Systemic toxicity of traditional chemotherapy drugs due to poor drug selectivity, and chemotherapy failure due to tumor drug resistance and other problems, so it is particularly important to find new cancer treatment strategies for TNBC with limited treatment options. Both the anti-tumor natural drugs curcumin and ginsenoside Rg3 can exert anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells, reducing PD-L1 expression, and reducing cancer stem cells. However, they have the disadvantages of poor water solubility, low bioavailability, and weak anti-tumor effect of single agents. We used vinyl ether bonds to link curcumin (Cur) with N-O type zwitterionic polymers and at the same time encapsulated ginsenoside Rg3 to obtain hyperbranched zwitterionic drug-loaded micelles OPDEA-PGED-5HA@Cur@Rg3 (PPH@CR) with pH response. In vitro cell experiments and in vivo animal experiments have proved that PPH@CR could not only promote the maturation of dendritic cells (DCs) and increase the CD4+ T cells and CD8+ T cells by inducing ICD in tumor cells but also reduce the expression of PD-L1 in tumor tissues, and reduce cancer stem cells and showed better anti-tumor effects and good biological safety compared with free double drugs, which is a promising cancer treatment strategy.

Effect of molecular crowders on ligand binding kinetics with G-quadruplex DNA probed by fluorescence correlation spectroscopy.

Guanine-rich single-stranded DNA folds into G-quadruplex DNA (GqDNA) structures, which play crucial roles in various biological processes. These structures are also promising targets for ligands, potentially inducing antitumor effects. While thermodynamic parameters of ligand/DNA interactions are well-studied, the kinetics of ligand interaction with GqDNA, particularly in cell-like crowded environments, remain less explored. In this study, we investigate the impact of molecular crowding agents (glucose, sucrose, and ficoll 70) at physiologically relevant concentrations (20% w/v) on the association and dissociation rates of the benzophenoxazine-core based ligand, cresyl violet (CV), with human telomeric antiparallel-GqDNA. We utilized fluorescence correlation spectroscopy (FCS) along with other techniques. Our findings reveal that crowding agents decrease the binding affinity of CV to GqDNA, with the most significant effect-a nearly three-fold decrease-observed with ficoll 70. FCS measurements indicate that this decrease is primarily due to a viscosity-induced slowdown of ligand association in the crowded environment. Interestingly, dissociation rates remain largely unaffected by smaller crowders, with only small effect observed in presence of ficoll 70 due to direct but weak interaction between the ligand and ficoll. These results along with previously reported data provide valuable insights into ligand/GqDNA interactions in cellular contexts, suggesting a conserved mechanism of saccharide crowder influence, regardless of variations in GqDNA structure and ligand binding mode. This underscores the importance of considering crowding effects in the design and development of GqDNA-targeted drugs for potential cancer treatment.

Combination of microparticles vaccine with MSI-1436 exerts a strong immune response for hepatocellular carcinoma.

Although tumor cell-derived microparticles (MPs) vaccines have reportedly induced anti-tumor immune reactions for various cancers, the mechanism by which MPs derived from Hepa1-6 cells are taken up by dendritic cells (DCs) and provide the MPs antigens message to CD8+ T cells to exert their anti-hepatocellular carcinoma (HCC) effects remain unclear. Furthermore, the role of MPs in combination with the small-molecule drug MSI-1436, an inhibitor of protein tyrosine phosphatase 1B (PTP1B), in HCC has not yet been reported. In this study, protein mass spectrometry combined with cytology revealed that MPs are mainly taken up by DCs via the clathrin-mediated endocytosis and phagocytosis pathway and localized mainly in lysosomes. High concentration of tumor necrosis factor (TNF)-α and interferon (IFN)-γ were detected in CD8+ T cells stimulated with MPs-loaded DCs. Moreover, MPs combined with MSI-1436 further suppressed the proliferation of HCC cells in C57BL/6 tumor-bearing mice, which was closely correlated with CD4+/CD8+ T cells counts in peripheral blood, spleen, and the tumor microenvironment. Mechanistically, the combination of MPs and MSI-1436 exerts a more powerful anti-HCC effect, which may be related to the further inhibition of the expression of PTP1B. Overall, MPs combined with MSI-1436 exerted stronger anti-tumor effects than MPs or MSI-1436 alone. Therefore, the combination of MPs and MSI-1436 may be a promising means of treating HCC.

Acetylsalicylic Acid with Ascorbate: A Promising Combination Therapy for Solid Tumors.

Cancer is a deadly disease with high mortality rates in developing countries. A recent preclinical study found promising results in treating hepatocellular carcinoma (HCC) by combining acetylsalicylic acid (ASA) and ascorbate (AS), which might offer a safer alternative to expensive clinical chemotherapeutics; however, the impact of this combination on other tumors remains unexplored. Therefore, this study aims to investigate the effectiveness of combining ASA and AS in treating Ehrlich solid tumors. Eighty female Swiss albino mice were divided into eight groups (10 mice/group): four healthy groups (healthy, AS, ASA, and AS+ASA) and four groups with carcinoma (Ehrlich ascites carcinoma [EAC], EAC+AS, EAC+ASA, and EAC+AS+ASA). AS was injected intraperitoneally (4g/kg) daily for 10 days, whereas ASA was ingested orally at 60 mg/kg/day for 10 days. Carcinoma was induced by subcutaneous injection of 1×106 EAC cells/mouse once. Treatment of carcinoma started after 10 days of tumor inoculation. Blood, livers, and tumors were obtained, and tumor weights, volumes, and levels of hemoglobin, aminotransferases, albumin, bilirubin, urea, creatinine, lipid profile, malondialdehyde, nitric oxide, glutathione, catalase, total antioxidant capacity, lactate dehydrogenase, and creatine kinase were estimated. The percentage increase in lifespan was also assessed. Tumor treatment alleviated tumor burden. Tumor size was reduced, lifespan increased, organs (liver, kidney, and heart) functions adjusted, hemoglobin, lipid profile improved, and oxidative stress decreased. Combining ASA with AS showed more effective antitumor effects than only ASA or AS alone. After more validation research, combining ASA with AS may provide benefit in cancer treatment.

Research progress on anti-cancer mechanism of salidroside regulating miRNA-mRNA signaling axis

Abstract MiRNA (MicroRNA) can target and regulate mRNA, thereby influencing the biological processes of tumors. The extract of Tibetan medicine Rhodiola demonstrates anti-tumor effects by targeting and regulating cancer-related signaling molecules and pathways. This review aims to pave the way for integrating salidroside into clinical practice, fully leverage its multi-effective and multi-targeted biological effects, and innovate approaches to tumor prevention and management, thus enhancing cancer prognosis. We initially delve into the occurrence and mechanism of action of miRNA, as well as the anti-tumor mechanism of the miRNA-mRNA signaling axis. Additionally, it was described that salidroside can hinder cancer cell proliferation by inducing autophagy and apoptosis, inhibiting cell metastasis and invasion, and modulating the tumor microenvironment and cell cycle. Moreover, examples from lung cancer, gastric cancer, and nasopharyngeal carcinoma confirm that salidroside regulates the onset and progression of tumors through the miRNA-mRNA signaling axis. This groundbreaking discovery carries significant implications for cancer diagnosis and treatment, offering a novel pathway for therapeutic intervention.

Extracellular vesicles enhance the in vivo antitumor effects of millettia species-derived compounds in chronic myelogenous leukemia therapy

Several Millettia species are being investigated as medicinal ingredients due to their promising anti-cancer and anti-inflammatory properties. However, the application of Millettia species-derived compounds has been severely hindered by their poor aqueous solubility, rapid metabolism, and low bioavailability. Extracellular vesicles (EVs), which as membrane-bound phospholipid vesicle initiatively secreted through a variety of mammalian cells, are increasingly recognized as promising drug delivery vehicles. Therefore, EVs are with great potential to enhance both the stability and efficacy of the Millettia species-derived compounds in treatment. In this study, extracellular vesicles derived from chronic myelogenous leukemia cells are developed for delivering the extracts of Millettia speciosa Champ and Millettia pachyloba Drake-derived Homobutein. Notably, Homobutein-loaded EV (hEV) formed a stable and homogenous nanosized particle with high entrapment efficiency up to 55.7%. Moreover, EVs loaded with Homobutein were significantly more potent than free drugs in inhibiting K562 cell proliferation. The results demonstrated that intravenous injection of EV loaded with Homobutein effectively inhibits tumor growth in tumor-bearing mice compared to free Homobutein. Hence, this strategy can effectively enhance the efficacy of Millettia species-derived drugs in chronic myelogenous leukemia therapy.

Ropivacaine synergizes with sorafenib to induce apoptosis of hepatocellular carcinoma cells via the IL-6/STAT3 pathway.

The development of resistance in hepatocellular carcinoma (HCC) cells limits the effectiveness of sorafenib, but combination therapy with other drugs may have a positive effect. However, the effect of ropivacaine combined with sorafenib on the treatment of HCC cells and its potential regulatory mechanisms remain unclear. The proliferation and apoptosis of HCC cells treated with ropivacaine, sorafenib, and ropivacaine plus sorafenib were analyzed by cell-counting kit 8 and flow cytometry. The protein levels were measured by Western blot. The antitumor effect of ropivacaine, sorafenib, and their combination was verified by a tumor xenograft model. Ropivacaine and sorafenib markedly impeded the viability of HCC cells in a concentration-dependent manner. Compared with ropivacaine or sorafenib treatment alone, ropivacaine and sorafenib combination treatment impeded HCC cell proliferation, facilitated apoptosis, enhanced cleaved caspase-3, cleaved caspase-9, and cyclin D1 protein expression, while it reduced IL-6 and p-STAT3 expression and inhibited tumor growth invivo. Importantly, the activation of the IL-6/STAT3 pathway could reverse the repressive or stimulative effects of ropivacaine and sorafenib on the proliferation and apoptosis in HCC cells. In summary, ropivacaine synergistically induces sorafenib-stimulated apoptosis of HCC cells via the IL-6/STAT3 pathway. Ropivacaine is a potential drug for the treatment of HCC when combined with sorafenib.

Total triterpenoids from apple peels exert pronounced anti-breast-cancer activity in vivo and in vitro.

Apples are among the most nutritionally valuable fruits and have a history of use in traditional Chinese medicine. Triterpenoids, the primary bioactive compounds found in apples, demonstrate significant antitumor activity. Following enrichment and optimization, the total content of major triterpenoids in total triterpenoids from apple peels (ATT) reached 5.76 g kg-1. The growth of MDA-MB-231 xenograft tumors was significantly inhibited after treatment with ATT. Network pharmacology analysis conclusively identified a close association between the antitumor effect of ATT and the phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway. Experimental validation using MDA-MB-231 cells and a xenograft nude mouse model confirmed that ATT suppressed tumor cell proliferation effectively by modulating the PI3K-Akt signaling pathway, which was consistent with the findings from network pharmacology. The total triterpenoids from apple peels also induced cell apoptosis by mediating the PI3K-Akt signaling pathway. The total triterpenoids from apple peels can inhibit tumor cell proliferation and induce cell apoptosis effectively through the PI3K-Akt signaling pathway, suggesting that ATT holds promise as a prospective therapeutic agent for breast cancer treatment. © 2024 Society of Chemical Industry.

Cordycepin Augments the Efficacy of Anti-PD1 against Colon Cancer

Colon cancer has a poor clinical response to anti-PD1 therapy. This study aimed to evaluate the effect of cordycepin on the efficacy of anti-PD1 treatment in colon cancer. The viability of CT26 mouse colon carcinoma cells, cell-cycle progression, morphology, and the expression of mRNA and protein were assessed. A syngeneic animal model was established by implanting CT26 cells into BALB/c mice for in vivo experiments. Multi-parameter flow cytometry was used to analyze the splenic cell lineages and tumor microenvironment (TME). The in vitro data revealed that cordycepin, but not adenosine, inhibited CT26 cell viability. The protein, but not mRNA, expression levels of A2AR and A2BR were suppressed by cordycepin but not by adenosine in CT26 cells. The combination of cordycepin, but not adenosine, with anti-PD1 exhibited a greater tumor-inhibitory effect than anti-PD1 alone as well as inhibited the expression of A2AR and A2BR in splenic macrophages. In the TME, the combination of cordycepin and anti-PD1 increased the number of CD3+ T cells and neutrophils and decreased the number of natural killer (NK) cells. Overall, cordycepin augmented the antitumor effects of anti-PD1 against mouse colon carcinoma cells and inhibited the expression of the adenosine receptors A2AR and A2BR in splenic macrophages and intratumoral NK cells.

Evaluation of a novel 177Lu-labelled therapeutic Affibody molecule with a deimmunized ABD domain and improved biodistribution profile.

Fusion of Affibody molecules with an albumin-binding domain (ABD) provides targeting agents, which are suitable for radionuclide therapy. To facilitate clinical translation, the low immunogenic potential of such constructs with targeting properties conserved is required. The HER2-targeting Affibody molecule ZHER2:2891 was fused with a deimmunized ABD variant and DOTA was conjugated to a unique C-terminal cysteine. The novel construct, PEP49989, was labelled with 177Lu. Affinity, specificity, and in vivo targeting properties of [177Lu]Lu-PEP49989 were characterised. Experimental therapy in mice with human HER2-expressing xenografts was evaluated. The maximum molar activity of 52 GBq/µmol [177Lu]Lu-PEP49989 was obtained. [177Lu]Lu-PEP49989 bound specifically to HER2-expressing cells in vitro and in vivo. The HER2 binding affinity of [177Lu]Lu-PEP49989 was similar to the affinity of [177Lu]Lu-ABY-027 containing the parental ABD035 variant. The renal uptake of [177Lu]Lu-PEP49989 was 1.4-fold higher, but hepatic and splenic uptake was 1.7-2-fold lower than the uptake of [177Lu]Lu-ABY-027. The median survival of xenograft-bearing mice treated with 21 MBq [177Lu]Lu-PEP49989 (> 90 days) was significantly longer than the survival of mice treated with vehicle (38 days) or trastuzumab (45 days). Treatment using a combination of [177Lu]Lu-PEP49989 and trastuzumab increased the number of complete tumour remissions. The renal and hepatic toxicity was minimal to mild. In preclinical studies, [177Lu]Lu-PEP49989 demonstrated favourable biodistribution and a strong antitumour effect, which was further enhanced by co-treatment with trastuzumab.

Ferroptosis crosstalk in anti-tumor immunotherapy: molecular mechanisms, tumor microenvironment, application prospects.

Immunotherapies for cancer, specifically immune checkpoint inhibition (ICI), have shown potential in reactivating the body's immune response against tumors. However, there are challenges to overcome in addressing drug resistance and improving the effectiveness of these treatments. Recent research has highlighted the relationship between ferroptosis and the immune system within immune cells and the tumor microenvironment (TME), suggesting that combining targeted ferroptosis with immunotherapy could enhance anti-tumor effects. This review explores the potential of using immunotherapy to target ferroptosis either alone or in conjunction with other therapies like immune checkpoint blockade (ICB) therapy, radiotherapy, and nanomedicine synergistic treatments. It also delves into the roles of different immune cell types in promoting anti-tumor immune responses through ferroptosis. Together, these findings provide a comprehensive understanding of synergistic immunotherapy focused on ferroptosis and offer innovative strategies for cancer treatment.

A Copper Silicate-Based Multifunctional Nanoplatform with Glutathione Depletion and Hypoxia Relief for Synergistic Photodynamic/Chemodynamic Therapy

Chemodynamic therapy (CDT) alone cannot achieve sufficient therapeutic effects due to the excessive glutathione (GSH) and hypoxia in the tumor microenvironment (TME). Developing a novel strategy to improve efficiency is urgently needed. Herein, we prepared a copper silicate nanoplatform (CSNP) derived from colloidal silica. The Cu(II) in CSNP can be reduced to Cu(I), which cascades to induce a subsequent CDT process. Additionally, benefiting from GSH depletion and oxygen (O2) generation under 660 nm laser irradiation, CSNP exhibits both Fenton-like and hypoxia-alleviating activities, contributing to the effective generation of superoxide anion radical (•O2−) and hydroxyl radical (•OH) in the TME. Furthermore, given the suitable band-gap characteristic and excellent photochemical properties, CSNP can also serve as an efficient type-I photosensitizer for photodynamic therapy (PDT). The synergistic CDT/PDT activity of CSNP presents an efficient antitumor effect and biosecurity in both in vitro and in vivo experiments. The development of an all-in-one nanoplatform that integrates Fenton-like and photosensing properties could improve ROS production within tumors. This study highlights the potential of silicate nanomaterials in cancer treatment.

METTL3-mediated m6A Modification of hsa_circ_0131922 Attenuates the Progression of Papillary Thyroid Cancer by Regulating the p53 Pathway.

This study aimed to confirm the regulatory role and mechanism of circular RNA (circRNA) hsa_circ_0131922 in Papillary Thyroid Carcinoma (PTC) progression. Accumulating evidence suggests that N6-methyladenosine (m6A)-modified circular RNAs (circRNAs) perform pivotal functions in various malignancies. However, the specific role of the m6A modification of circRNA mediated by METTL3 in Papillary Thyroid Carcinoma (PTC) remains undocumented. In this work, we aimed to examine the molecular mechanisms of a novel m6Amodified circRNA, hsa_circ_0131922, in PTC progression. Potential circRNA was identified from GEO datasets. The RNA or protein levels of hsa_circ_0131922, METTL3, p53, and p21 were evaluated by qRT-PCR or western blot assays. The various cellular functions were checked by CCK8, wound healing, transwell, and xenograft tumor assays. MeRIP-qPCR was performed to observe the METTL3-mediated m6A modification of hsa_circ_0131922. Furthermore, the interactions between hsa_circ_0131922 and METTL3 in PTC were analyzed by bioinformatics analysis and various rescue experiments. The levels of hsa_circ_0131922 were markedly downregulated in PTC tissues and cell lines. In addition, the lower hsa_circ_0131922 levels correlated with poor prognosis in PTC patients. The hsa_circ_0131922 overexpression reduced the malignant phenotypes of PTC cells and activated the p53/p21 pathway. Bioinformatic analysis showed the m6A-modified sites of hsa_circ_0131922, and a positive correlation between hsa_circ_0131922 and METTL3. Moreover, overexpression of METTL3 increased the levels of m6A modification of hsa_circ_0131922. Mechanistically, the anti-tumor effects of hsa_circ_0131922 overexpression have been found to be partially reversed by silencing METTL3 in vivo and in vitro. The results have demonstrated m6A-modified hsa_circ_0131922 by METTL3 to attenuate the progression of PTC by regulating the p53 pathway. Therefore, hsa_circ_0131922 could be a predictive prognostic biomarker and therapeutic target for PTC.

α-Lactalbumin mRNA-LNP Evokes an Anti-Tumor Effect Combined with Surgery in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) has been considered a huge clinical unmet need due to its aggressive progression and highly frequent metastasis. mRNA therapeutics supply a potential and versatile immunotherapy of oncology treatment. Here, we developed α-lactalbumin mRNA-lipid nanoparticles (α-LNP) as a potential therapeutical strategy for TNBC. The α-LNP induced the specific IgG antibodies and activated IFN γ-secreting-T cells in vivo. Additionally, the safety of α-LNP also had been demonstrated in vivo. When vaccinated prior to tumor implantation, α-LNP showed a preventive effect against 4T1 tumor growth and extended the survival of the tumor model by activating the memory immune responses. Furthermore, α-LNP administration in combination with surgical removal of neoplasm effectively inhibited the progression and metastasis in the TNBC model. Taken together, our results indicate that the α-LNP vaccine is a promising novel treatment for both therapeutics and prophylactics in TNBC.

Natural Killer-Based Therapy: A Prospective Thought for Cancer Treatment Related to Diversified Drug Delivery Pathways

Immunotherapy has been a research hotspot due to its low side effects, long-lasting efficacy, and wide anti-tumor spectrum. Recently, NK cell-based immunotherapy has gained broad attention for its unique immunological character of tumor identification and eradication and low risk of graft-versus-host disease and cytokine storm. With the cooperation of a drug delivery system (DDS), NK cells activate tumoricidal activity by adjusting the balance of the activating and inhibitory signals on their surface after drug-loaded DDS administration. Moreover, NK cells or NK-derived exosomes can also be applied as drug carriers for distinct modification to promote NK activation and exert anti-tumor effects. In this review, we first introduce the source and classification of NK cells and describe the common activating and inhibitory receptors on their surface. Then, we summarize the strategies for activating NK cells in vivo through various DDSs. Finally, the application prospects of NK cells in tumor immunotherapy are also discussed.

Biomimetic liposome amplifying mitochondrial damage to potential cancer radio-immunotherapy

Radiotherapy, despite its precision and non-invasiveness, often fails due to the resistance of cancer stem cells (CSCs), which are characterized by high self-renewal capabilities and superior DNA repair mechanisms. These cells can evade RT and lead to tumor recurrence and metastasis. To address this challenge, a novel delivery system named PB has been introduced. This system combines liposomes with platelet membranes to encapsulate Bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl) ethyl sulfide (BPTES), thus enhancing its delivery and release specifically at tumor sites. In addition, this system not only targets CSCs effectively but also increases the local concentration of BPTES upon X-ray irradiation, which reduces glutathione levels in tumor cells, thereby increasing oxidative stress and damaging mitochondria. PB-elicited mitochondrial damage as the STING signal initiator, which mediated significant upregulation in the expression of a cGAS-STING pathway-related protein thereby amplifying the STING signal. Systemic intravenous administration of PB remarkably promoted DC maturation and CD8+ T cell infiltration, thus eliciting strong antitumor effects. Overall, this PB system presents a potent method to overcome CSC-related resistance and offers a promising approach for future cancer treatment protocols.