Target Cancer Cells Research Articles

Chitosan-based hydrogels in cancer therapy: Drug and gene delivery, stimuli-responsive carriers, phototherapy and immunotherapy

Nanotechnology has transformed the oncology sector by particularly targeting cancer cells and enhancing the efficacy of conventional therapies, not only improving efficacy of conventional therapeutics, but also reducing systemic toxicity. Environmentally friendly materials are the top choice for treating cancer. Chitosan, sourced from chitin, is widely used with its derivatives for the extensive synthesis or modification of nanostructures. Chitosan has been deployed to develop hydrogels, as 3D polymeric networks capable of water absorption with wide biomedical application. The chitosan hydrogels are biocompatible and biodegradable structures that can deliver drugs, genes or a combination of them in cancer therapy. Increased tumor ablation, reducing off-targeting feature and protection of genes against degradation are benefits of using chitosan hydrogels in cancer therapy. The efficacy of cancer immunotherapy can be improved by chitosan hydrogels to prevent emergence of immune evasion. In addition, chitosan hydrogels facilitate photothermal and photodynamic therapy for tumor suppression. Chitosan hydrogels can synergistically integrate chemotherapy, immunotherapy, and phototherapy in cancer treatment. Additionally, chitosan hydrogels that respond to stimuli, specifically thermo-sensitive hydrogels, have been developed for inhibiting tumors.

STK33 as the functional substrate of miR-454-3p for suppression and apoptosis in neuroblastoma

miR-454-3p has been reported to be a tumor suppressive micro-RNA (miRNA) in multiple cancer types. We identified the kinase STK33 mRNA, which is a high-risk factor for survival in neuroblastoma (NB) patients, as being a substrate of miR-454-3p in NB. Even though STK33 is an attractive target for several cancers, development of inhibitors of STK33 has been challenging. For the various cell lines tested, we demonstrated reduced growth and viability with the miR-454-3p mimic. From among the candidate NB-associated miRNAs, miR-454-3p mimic and its antagonist had the most profound effect on STK33 mRNA and protein level changes. Under various conditions of growth and external stress for the cells, the RNA levels for miR-454-3p and STK33 also negatively correlated. Luciferase reporter assays demonstrated STK33 as a substrate for miR-454-3p, and recombinant versions of STK33 resistant to miR-454-3p significantly blunted the suppressive effect of the miR-454-3p and established STK33 as the major functional substrate of miR-454-3p. Overexpression of miR-454-3p or knockdown of STK33 mRNA promoted autophagy, and at the same time, increased the apoptotic markers in the tested NB cells, indicating a mechanism for the suppressive effect of the agents. Given the difficult-to-drug targets such as STK33 and the recent successes in RNA delivery methods for cancer treatment, it is thought that targeting cancer cells with a suppressive miRNA such as miR-454-3p for STK33-dependent cancer types may be an alternative means of NB therapy.

The Combined Effect of Hypoxia Activation and Radiosensitization by a Multifunctional Nanoplatform System Enhances the Therapeutic Efficacy of Chemoradiotherapy in Pancreatic Cancer

BackgroundPancreatic cancer is a highly malignant tumor, which is still a major global health problem. Chemotherapy and radiotherapy are regularly used in adjuvant therapy for pancreatic cancer but their therapeutic efficacy is limited. MethodsIn the present study, nanoparticle（MSN-AuNPs） was used as a drug carrier loaded with tirapazamine(TPZ) and hyaluronic acid (HA) to synthesize a multifunctional nanoplatform HA@TPZ-MSN-AuNPs (HTMA) for hypoxia activation and radiotherapy sensitization, which can be combined with radiotherapy therapy and synergistically enhance the therapeutic effect in pancreatic cancer. The anti-tumor performance of the nano platform was verified by in vivo and in vitro experiments. ResultFirst, the HA@TPZ-MSN-AuNPs (HTMA) was successfully synthesized. Drug release experiments showed that acidic environment and hyaluronidase promoted drug release in the nanoplatform. In vitro experiments, CCK-8, live-dead staining, clonal formation assay and flow cytometry confirmed the combined anti-tumor effect of hypoxia activation and radiotherapy sensitization with HTMA. In the drug uptake experiment, the nanoplatform showed the function of targeting and binding pancreatic cancer cells. In vivo, HTMA demonstrated good antitumor properties and good biocompatibility. ConclusionsThe nanoplatform had a good targeting effect and synergistic anti-tumor effect. The combination of hypoxia activation and radiotherapy sensitization is a promising strategy for the treatment of pancreatic cancer.

Cancer Stem Cells and Treatment of Cancer: An Update and Future Perspectives.

Cancer stem cells (CSCs) play an essential role in tumour progression and metastasis. Stem cell ability of self-renewal enables it to persist over time, thereby contributing to cancer relapse or recurrence and also resistance to current therapies. Therefore, targeting CSCs emerged as a promising strategy of cancer treatment. CSCs exhibit differentiation, self-renewal, and plasticity, they contribute to formation of malignant tumours, also favors, metastasis, heterogeneity, multidrug resistance, and radiation resistance. Coventional cancer treatments predominantly target cancer cells that are not CSCs, CSCs frequently survive, eventually leading to relapse. This article focuses on the development of novel therapeutic strategies that combine conventional treatments and CSC inhibitors to eradicate cancer cells and CSCs, for the better and permanent treatment. However, the diversity of CSCs is a significant obstacle in the development of CSC-targeted therapies, necessitating extensive research for a better understanding and exploration of therapeutic approaches. Future development of CSC-targeted therapies will rely heavily on overcoming this obstacle.

Immunogenic properties of nickel-doped maghemite nanoparticles and the implication for cancer immunotherapy

Nanoparticles are commonly used in diagnostics and therapy. They are also increasingly being implemented in cancer immunotherapy because of their ability to deliver drugs and modulate the immune system. However, the effect of nanoparticles on immune cells involved in the anti-tumor immune response is not well understood. The study reported here showed that nickel-doped maghemite nanoparticles (FN NP) are differentially cytotoxic to cultured mouse and human cancer cell lines, causing their death without negatively impacting the subsequent anticancer immune response. It also found that FN NP induced cell death in the mouse colorectal cancer cell line CT26 and human prostate cancer cell line PC-3, but not in the human prostate cancer cell line LNCaP. The induced cancer cell death did not affect the phenotype and responsivity of the isolated mouse peritoneal macrophages, or ex vivo-generated mouse bone marrow-derived, or human monocyte-derived dendritic cells. Additionally, the induced cancer cell death did not prevent the ex vivo-generated mouse or human dendritic cells from stimulating lymphocytes and enriching cell cultures with cancer cell-reactive T-cells. In conclusion, this study shows that FN NP could be a valuable platform for targeting cancer cells without causing immunosuppressive effects on the subsequent anticancer immune response.

Exploring the Anticancer Potential of Triazine Derivatives: An Outlook of Designing Strategies, Docking Studies, and Structure‐Activity Relationships (SAR)

AbstractCancer is a disease characterized by uncontrolled cell growth resulting from genetic and epigenetic changes accumulating within a cancer cell population. Despite the milestone discovery of chemotherapeutic drugs against cancer, cancer remains tough to cure. Therefore, cancer has the second‐highest global death rate. There are certain factors such as genetic mutation, cancer cell diversity, metastasis, and resistance, which limit chemotherapy. To combat cancer, it's crucial to find novel therapeutic tactics and produce novel drugs that target cancer cells without affecting healthy cells. Heterocyclic compounds influence certain molecular targets to find novel lead structures can be a noteworthy strategy for the development of potential anticancer agents. Triazine, a low‐cost and widely available heterocyclic scaffold, has piqued researchers’ interest in developing innovative designing strategies. This review presents the advancement of three different isomers of triazines as anticancer agents. The main focus of this review is to provide the advancement of designing strategies, structure‐activity relationships, and docking studies of triazine derivatives as anticancer agents the available triazine‐containing drugs, and the status of clinical trials of triazine‐containing drugs were also highlighted. Lastly, we have also concluded the most potent derivatives and their hybridization with another ring to justify the particular anticancer activity.

Oxidative phosphorylation related gene COA6 is a novel indicator for the prognosis and immune response in lung adenocarcinoma

Although the initial research focused on glycolysis, mitochondrial oxidative phosphorylation has become a major target of cancer cells. Cytochrome C oxidase assembly factor 6 (COA6) is a conserved assembly factor necessary for complex IV biogenesis. Nevertheless, the clinical predictive value of COA6, especially its correlation with immune cell infiltration in lung adenocarcinoma (LUAD), has not yet been elucidated. COA6 exhibited higher expression levels in LUAD cells and tumor tissues compared to normal tissues. Additionally, heightened COA6 expression was associated with reduced overall survival (OS) and advanced tumor stage. Apart from its role in mitochondrial respiratory processes, COA6 may be involved in the process of antigen binding, immunoglobulin receptor binding. Interestingly, we observed a positive correlation between COA6 expression and tumor mutational burden (TMB), as well as a significant association with decreased immune cell infiltration. COA6 was linked to resistance against gemcitabine and etoposide. We verified that COA6 was highly expressed in LUAD experimentally and cell proliferation was inhibited after COA6 knockdown. Thus, we conclude that the expression of COA6 was correlated with reduced immune cell infiltration. Additionally, COA6 functioned as a biomarker for drug sensitivity and the prognosis of lung adenocarcinoma.

Beyond ADCs: harnessing bispecific antibodies to directly induce apoptosis for targeted tumor eradication

Abstract Bispecific apoptosis triggers (BATs) are innovative bispecific antibodies designed to simultaneously target both a tumor-associated antigen and a cancer cell’s death receptor, thereby directly activating the extrinsic apoptotic pathway to induce death of cancer cells. This unique mechanism distinguishes BATs from antibody-drug conjugates (ADCs), which rely on cytotoxic drugs, and bispecific immune cell engagers such as bispecific T-cell engagers (BiTEs) and bispecific natural killer cell engagers (NKCEs), which recruit immune cells to eliminate target cancer cells. BATs offer significant potential advantages in clinical efficacy and safety over ADCs and BiTEs. Although the field is still emerging, recent advancements are highly promising, and analysis of preclinical and clinical data of DR5-targeting antibodies have been pivotal in outlining the criteria for the next generation of effective and safe medicines. Antibodies found inactive in preclinical testing were also found to be clinically ineffective, whereas antibodies with minimal preclinical results demonstrated moderate clinical activity. All clinical DR5-targeting antibodies were well tolerated by patients even at high doses (with the exception of TAS266 due to its unique design). These findings underscore the predictive value of robust preclinical models on clinical outcomes. Notably, first-in-class BAT, Cancerlysin™ IMV-M, demonstrated potent efficacy in diverse xenograft cancer models and safety in non-human primates, marking a significant advancement in developing safe and effective anti-cancer drugs.

Zn(II)-Curcumin Complexes-Based Anticancer Agents.

There is a great deal of research interest in the design of alternative metallodrugs to Pt(II)-derivatives for cancer treatment. The low solubility of such drugs in biological mediums leading to poor bioavailability is the major hurdle of several metal-based anticancer agents. These issues have recently been addressed by designing bio-active ligands based on metal-containing anticancer agents. Conjugating with bioactive ligands has significantly improved the bioavailability of the metallodrugs and their cancer cell targeting ability. One such naturally available bioactive ligand is curcumin. Until recently, several curcumin-based anticancer metallodrugs have been developed and successfully demonstrated for their anticancer studies. In this article, we aim to highlight, the synthesis, structure, and anticancer properties of various Zn(II)-curcumin-based coordination complexes. The effect of introducing different functional groups, targeting ligands, and photo-active ligands on the anticancer potential of such complexes has been mentioned in detail. The current status and future perspective on curcumin-based metallodrugs for cancer treatment have also been stated.

GULP1 as a Downstream Effector of the Estrogen Receptor-β Modulates Cisplatin Sensitivity in Bladder Cancer.

Precise molecular mechanisms underlying resistance to cisplatin-based chemotherapy remain unclear, while the activity of estrogen receptor-β (ERβ) has been suggested to be associated with chemosensitivity in urothelial cancer. We aimed to determine if GULP1, an adapter protein known to facilitate phagocytosis, could represent a downstream effector of ERβ and thereby modulate cisplatin sensitivity in bladder cancer. GULP1 expression and cisplatin cytotoxicity were compared in bladder cancer lines. Immunohistochemistry was used to determine the expression of GULP1 and ERβ in two sets of tissue microarray (TMA) consisting of transurethral resection specimens. The levels of GULP1 expression were considerably higher in ERβ-knockdown sublines than in the respective control ERβ-positive sublines. Estradiol treatment reduced GULP1 expression in ERα-negative/ERβ-positive lines, which was restored by the anti-estrogen tamoxifen. Chromatin immunoprecipitation assay revealed the binding of ERβ to the GULP1 promoter in bladder cancer cells. Moreover, GULP1 knockdown sublines were significantly more resistant to cisplatin treatment, but not to other chemotherapeutic agents, including gemcitabine, methotrexate, vinblastine, and doxorubicin. In the first set of TMA (n=129), the expression of ERβ and GULP1 was inversely correlated (p=0.023), and ERβ(-)/GULP1(+) in 51 muscle-invasive tumors was associated with significantly lower risk of disease progression and cancer-specific mortality. Similarly, in the second set (n=43), patients with ERβ(-)/GULP1(+) muscle-invasive disease were significantly (p=0.021) more likely to be responders to cisplatin-based neoadjuvant chemotherapy before radical cystectomy. ERβ activation was found to reduce the expression of GULP1 as a direct downstream target in bladder cancer cells, resulting in the induction of cisplatin resistance.

IL-12 encoding oNDV synergizes with CAR-T cells in orthotopic models of non-small cell lung cancer

Systemic administration of oncolytic viruses (OVs) is a promising approach for targeting metastatic solid tumors, but their anti-tumor activity is limited by pre-existing neutralizing antibodies against common human viruses. Therefore, investigators have developed OVs derived from non-human host viruses. Successful implementation of this strategy requires that the viral vector selectively infects and replicates within human cancer cells. Newcastle disease virus (NDV) is an avian paramyxovirus that as NDV-based OVs (oNDVs) have demonstrated safety and activity against multiple human tumors in clinical trials. Their use as a single agent, however is insufficient to cure tumors. Similarly, CAR-T cells enable systemic targeting of cancer cells but have limited anti-tumor effects against bulky solid tumors, in part due to the immunosuppressive tumor environment. In this study, we evaluated the anti-tumor effects of combining systemic oNDV and CAR-T cell treatments. In models of non-small cell lung carcinoma (NSCLC), we found that oNDV itself and IL-12 derived from oNDV enhance HER2-directed CAR-T cell anti-tumor activity and persistence in vitro and in vivo, leading to superior control of NSCLC tumors compared with either agent alone in vivo. Our data indicate that oNDV enhances the anti-tumor effects of HER2.CAR-T cells, thus controlling the growth of orthotopic NSCLC tumors.

Antibody-drug Conjugates in The Management of Advanced Urothelial Carcinoma

For decades, the cornerstone for treatment of advanced urothelial carcinoma (aUC) has consisted of platinum-based chemotherapy regimens, such as GC (gemcitabine plus cisplatin/carboplatin) or MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin). Thereafter, immune checkpoint inhibitors (ICI) were incorporated into the standard of care, initially as monotherapy in subsequent-line settings and more recently as maintenance treatment with chemotherapy in the first-line setting. Recently, the development of antibody-drug conjugates (ADCs) has dramatically shifted the treatment landscape for aUC. ADCs are engineered to function as a biologic “honing missile”, with the aim of delivering its cytotoxic payload to the target cancer cell while remaining stable in circulation and minimizing off-target toxicity. Enfortumab vedotin was the first to demonstrate efficacy in urothelial carcinoma (UC), initially as monotherapy and later in combination with ICI, surpassing the decades-old standard of first-line chemotherapy. The aim of this review is to discuss the evolving field of ADCs in aUC, highlighting the main targets, clinical data, toxicities, and future opportunities. ADCs are engineered to function as a biologic “honing missile”, with the aim of delivering its cytotoxic payload to the target cancer cell while remaining stable in circulation and minimizing off-target toxicity. Enfortumab vedotin was the first to demonstrate efficacy in urothelial carcinoma (UC), initially as monotherapy and later in combination with ICI, surpassing the decades-old standard of first-line chemotherapy. The aim of this review is to discuss the evolving field of ADCs in aUC, highlighting the main targets, clinical data, toxicities, and future opportunities.

Sacituzumab Govitecan in Triple Negative Breast Cancer: A Systematic Review of Clinical Trials.

Triple-negative breast cancer is difficult to treat due to the absence of hormone receptors and Her2neu. Sacituzumab govitecan is a new therapeutic approach that uses an antibody directed against the Trop-2 antigen present in solid epithelial tumors, linked to the active metabolite SN-38, similar to irinotecan, to specifically target cancer cells while minimizing damage to healthy cells. The objective of the present review was to evaluate the efficacy and safety of sacituzumab govitecan as a single treatment in patients with triple-negative breast cancer and to compare its results with the standard conventional chemotherapy regimen currently used in this disease. A systematic review of randomized clinical trials of sacituzumab govitecan was performed. The search was performed in Medline (PubMed), Web of Science, and Cochrane from September 2022 to January 2024. Thirty-eight articles are included and evaluated according to inclusion and exclusion criteria corresponding to the two most relevant clinical trials, including specific analyses of cohorts and subgroup study arms within these trials. Data from more recent clinical trials are also reviewed. The efficacy results showed a significantly greater clinical benefit with sacituzumab govitecan compared to standard chemotherapy in patients with triple-negative breast cancer. This drug will become a treatment of substantial impact in future treatment guidelines for this type of cancer.

Combining Phototherapy and Gold-Based Nanomaterials: A Breakthrough in Basal Cell Carcinoma Treatment.

Basal cell carcinoma (BCC) is the most common type of skin carcinoma worldwide. BCC development is the result of a complex interaction between environmental, phenotypic, and genetic factors. While conventional treatments such as surgery and topical therapies have demonstrated variable efficacy (some of them with limited efficacy), they are not free of adverse side effects, most of them debilitating. Thus, there is a notable gap in the literature regarding alternative and non-invasive therapeutic options. This review aims to address this gap, exploring the potential of photothermal therapy (PTT) combined with metallic nanoparticles, namely gold nanoparticles (AuNPs), as a minimally invasive treatment approach. Through a comprehensive review of the literature in the period from 2014 to 2024, using experimental investigations, this review seeks to elucidate the intricate interplay between genetic factors, environmental influences, and the tumor microenvironment in BCC disease progression, with PTT as a potential therapeutic strategy. Those studies confirmed an enhanced targeting of cancer cells and selective ablation of tumor tissue, using emerging technologies like PTT. A significant tumor reduction, often exceeding 50%, was observed, with some studies reporting complete elimination of the tumor. The main adverse effects noted were localized skin irritation and transient hyperpigmentation, but these were generally minimal and manageable, highlighting the promise of PTT as an effective treatment. Thus, by leveraging the unique properties of AuNPs to enhance the effectiveness of PTT, the targeting of cancer cells can more precisely occur, reducing collateral damage to healthy tissues. This approach not only aims to achieve better clinical results, but also contributes to the broader knowledge base in the field of BCC research. Continued research and clinical trials will be crucial in refining those techniques and validating their efficacy, ultimately paving the way for more effective and less invasive treatments for BCC.

Smart Cancer-Targeting and Super-Sensitive Sensing of Eu3+/Tb3+-Induced Hyaluronan Characteristic Nano-Micelles with Effective Drug Loading and Release.

To avoid the critical problems of effective drugs not being carried to their targeted cancers and their quantity and location not being sensed in situ, this work presents a completely new innovative strategy to achieve both smart cancer targeting (SCT) and super-sensitive sensing (SSS), where one drug carrier works for effective drug loading and release. Herein, malignant melanoma treatment is used as an example of reliable detection and effective therapy. We report two characteristic dumbbell-like nano-micelles and spherical-like nano-micelles of hyaluronan induced by the Eu3+/Tb3+ complexes for effective drug loading and release, respectively. These special Eu3+/Tb3+-loaded nano-micelles (marked as ENM and TNM) have strong and sharp red/green luminescence that can sensitively detect the malignant melanoma drug dacarbazine through changes in fluorescence intensity. Cytotoxicity experiments confirmed that both ENM and TNM are not toxic to normal cells at very high concentrations of 4 mM. However, when loaded with cancer drugs (D-ENM and D-ENM), they both killed cancer cells with more than 40% efficacy at this concentration. The in vivo experiments confirmed that D-ENM and D-TNM can effectively target cancer cells in tissue and effectively impede cancer growth. The detection limits of ENM and TNM in sensing cancer drugs can reach 0.456 μg/mL and 0.139 μg/mL, respectively. Therefore, the reported Eu3+/Tb3+-induced hyaluronan nano-micelles (ENM and TNM) are distinguished carriers of this cancer drug and excellent in situ sensors, and they have highly therapeutic effects with extremely low toxicity to normal cells.

Selective Recruitment of Antibodies to Cancer Cells and Immune Cell-mediated Killing via In Situ Click Chemistry.

Many current cancer immunotherapies function by redirecting immune system components to recognize cancer biomarkers and initiate a cytotoxic attack. The lack of a universal tumor biomarker limits the therapeutic potential of these approaches. However, one feature characteristic of nearly all solid tumors is extracellular acidity. This inherent acidity provides the basis for targeted drug delivery via the pH-low insertion peptide (pHLIP), which selectively accumulates in tumors in vivo due to a pH-dependent membrane insertion propensity. Previously, we established that we could selectively decorate cancer cells with antigen-pHLIP conjugates to facilitate antibody recruitment and subsequent killing by engineered effector cells via antibody-dependent cellular cytotoxicity (ADCC). Here, we present a novel strategy for opsonizing antibodies on target cell surfaces using click chemistry. We utilize pHLIP to facilitate selective tetrazine - trans-cyclooctene ligation of human IgGs to the cancer cell surface and induce ADCC. We demonstrate that our approach activates the primary ADCC signaling pathway via CD16a (FcγRIIIa) receptors on effector cells and induces the killing of cancer cell targets by engineered NK cells.

Two-Dimensional MXene (Ti3C2Tx)-based Nano-Photosensitizers for Enhanced Photothermal Ablation of Tumor Cells

Cancer remains one of the leading causes of death globally, accounting for approximately one in every six deaths. Traditional cancer therapies, including surgery, chemotherapy, chemoimmunotherapy, and radiation, face numerous challenges and limitations. In this context, we explore the advantages of photothermal therapy (PTT) using two-dimensional (2D) MXene-based nanocomposites for cancer treatment. MXenes, composed of abundant and non-toxic elements, such as titanium (Ti), carbon (C), fluorine (F), and oxygen (O), demonstrate low toxicity and are promising candidates in photothermal cancer therapies. Their ultrathin planar nanostructure, high photothermal conversion efficiency, strong near-infrared (NIR) responsiveness, and chemically modifiable surfaces enhance their therapeutic potential. Recent innovations include the development of folic acid-functionalized Au@c-Ti3C2 nanostructures, a skin-mountable electrostimulation patch (eT-patch), ionic gels containing MXene (Ti3C2Tx), and composite scaffolds made of MXene, collagen, silk fibroin, and quercetin. These MXene-based photosensitive compounds offer efficient targeting and selective treatment of cancer cells, highlighting their significant role in advancing cancer therapies.

Metal Peroxide Nanoparticles for Modulating the Tumor Microenvironment: Current Status and Recent Prospects.

Background: The significant expansion of nanobiotechnology and nanomedicine has led to the development of innovative and effective techniques to combat various pathogens, demonstrating promising results with fewer adverse effects. Metal peroxide nanoparticles stand out among the crucial yet often overlooked types of nanomaterials, including metals. These nanoparticles are key in producing oxygen (O2) and hydrogen peroxide (H2O2) through simple chemical reactions, which are vital in treating various diseases. These compounds play a crucial role in boosting the effectiveness of different treatment methods and also possess unique properties due to the addition of metal ions. Methods: This review discusses and analyzes some of the most common metal peroxide nanoparticles, including copper peroxide (CuO2), calcium peroxide (CaO2), magnesium peroxide (MgO2), zinc peroxide (ZnO2), barium peroxide (BaO2), and titanium peroxide (TiOx) nanosystems. These nanosystems, characterized by their greater potential and treatment efficiency, are primarily needed in nanomedicine to combat various harmful pathogens. Researchers have extensively studied the effects of these peroxides in various treatments, such as catalytic nanotherapeutics, photodynamic therapy, radiation therapy, and some combination therapies. The tumor microenvironment (TME) is particularly unique, making the impact of nanomedicine less effective or even null. The presence of high levels of reactive oxygen species (ROS), hypoxia, low pH, and high glutathione levels makes them competitive against nanomedicine. Controlling the TME is a promising approach to combating cancer. Results: Metal peroxides with low biodegradability, toxicity, and side effects could reduce their effectiveness in treating the TME. It is important to consider the distribution of metal peroxides to effectively target cancer cells while avoiding harm to nearby normal cells. As a result, modifying the surface of metal peroxides is a key strategy to enhance their delivery to the TME, thereby improving their therapeutic benefits. Conclusions: This review discussed the various aspects of the TME and the importance of modifying the surface of metal peroxides to enhance their therapeutic advantages against cancer, as well as address safety concerns. Additionally, this review covered the current challenges in translating basic research findings into clinical applications of therapies based on metal peroxide nanoparticles.

Synergistic chemo-photothermal anticancer effect of pH-responsive curcumin loaded mesoporous silica decorated reduced graphene

Synergistic chemo-photothermal therapy is employed to treat cancer. In this work, the curcumin loaded mesoporous silica on reduced graphene oxide (Cur-mSiO2@rGO) is synthesized. The mSiO2@rGO nanocarrier combines rGO to absorb NIR radiations with mSiO2 to load the drug. The mSiO2@rGO thus functions as bimodal photothermal agent and pH-responsive drug nanocarrier. Curcumin loaded onto the nanocarrier possesses antiproliferative, antioxidant, anti-inflammatory, pro-apoptotic, and antiangiogenic characteristics. It has anticancer potential against malignancies of stomach, liver, breast, lungs, and prostate. Breast cancer (BCa) is a major health concern worldwide. Curcumin inhibits BCa by mechanisms including apoptosis, cell cycle arrest, and modulation of signaling pathways. Moreover, curcumin blocks transcription factor (NF-κB), PI3K/AKT signaling, and STAT3 protein to inhibit liver cancer cell growth and survival. Cur-mSiO2@rGO targets cancer cells with enhanced loading capacity of 92 ± 1.02 % curcumin which is specifically released in the acidic tumor environment. NIR lamp irradiation at 808 nm ablates cancer cells to demonstrate the high photothermal conversion efficiency of rGO. In vitro experiments prove that synergistic chemo-photothermal therapy effectively kills cancer cells (HepG2 and MCF-7) compared to the single chemotherapeutic treatment. The toxicity of Cur-mSiO2@rGO is analyzed in vivo by the serum biochemical analysis, and biosafety by histopathological examination of vital body organs. A 1000 mg/kg specific dose of Cur-mSiO2@rGO shows no toxic effect on mice organs. Additionally, the in vivo studies confirm that Cur-mSiO2@rGO with NIR reduces tumor growth. Therefore, the multifunctional Cur-mSiO2@rGO can be a safe chemopreventive nanocarrier in tumor management and cancer photothermal therapy.

A select thiosemicarbazone copper(II) complex induces apoptosis in gastric cancer and targets cancer stem cells reducing pluripotency markers

Copper(II)-based complexes are promising candidates as anti-cancer agents due to their ability to target cancer cells. Here we describe the synthesis and characterization of two copper(II) thiosemicarbazone complexes with the ligands 4-(dimethylamino)benzaldehyde N4-methylthiosemicarbazone (HL1) and 4-(dimethylamino)benzaldehyde N4-(4-(dimethylamino)phenylthiosemicarbazone (HL2) and general formula [Cu(L)2]. The complexes show stability in aqueous solution with 1 % of DMSO that allows to stablish its solution profile in biological buffers. Compound [Cu(L1)₂] lipophilicity was lower than [Cu(L2)₂], however, its solubility in biological buffer was not only better but also its DLS and ζ-potential data. In vitro studies demonstrate a higher cytotoxic effect of [Cu(L1)₂] on gastric cancer cells. The proposed mechanism of action consists in the generation of free radicals that induce DNA lesions, oxidative stress and ultimately autophagy deregulation and apoptosis. Additionally, [Cu(L1)₂] is equally active on gastric cancer stem cells and tumor cells resistant to cisplatin. More importantly, stem cells treated with [Cu(L1)₂] show a downregulation of pluripotency markers such as TWIST, NANOG and OCT4. Overall, our results with [Cu(L1)₂] prompt a significant advancement in the development of rational-designed pharmaceuticals for combating cancer.