Eradicate Cancer Cells Research Articles

Nanotechnology in Cancer Therapy: A Paradigm Shift in Oncology

The application of nanotechnology in cancer therapy has revolutionized oncology by enabling precise, targeted, and minimally invasive treatment modalities. Nanoparticles, with their unique physicochemical properties, have emerged as versatile tools for improving drug delivery, imaging, and therapeutic efficacy. This review explores the role of nanotechnology in overcoming traditional challenges in cancer treatment, such as systemic toxicity, poor bioavailability, and resistance to chemotherapy. Key advancements include the development of multifunctional nanoparticles capable of simultaneous drug delivery and diagnostic imaging, as well as nanoscale systems designed to bypass biological barriers and deliver therapeutics directly to tumor sites. Additionally, nanotechnology has paved the way for innovative approaches like photothermal and photodynamic therapies, which harness light-mediated mechanisms to eradicate cancer cells with minimal damage to healthy tissues. Despite these advancements, challenges such as nanoparticle biocompatibility, scalability, and regulatory approval remain critical hurdles to widespread clinical adoption. This review provides a comprehensive overview of the current state of nanotechnology in cancer therapy, highlights its transformative potential, and discusses future directions for research and clinical translation. By bridging the gap between engineering and medicine, nanotechnology promises to redefine cancer care and improve patient outcomes

Abstract IA01: Moving forward translation of targeted therapy with external beam radiation

Radiotherapy is an anatomically highly targeted treatment modality capable of eradicating cancer cells, including cancer stem cells (CSC). This precision makes radiotherapy an ideal partner for synergistic treatment with targeted drugs, combining local effects on the tumor with systemic molecular interventions. To evaluate the efficacy of such combined treatments on inactivation of CSC in translational research, it is essential to select the appropriate clinical endpoints for preclinical experiments, most importantly inactivation of CSC in vitro or local tumor control in vivo. This ensures that preclinical findings are better translatable to the clinical setting, bridging the gap between experimental models and patient outcomes. A critical factor in this translational pipeline is the use of appropriate in vitro and animal or explant models that as accurate as possible mimic the clinical tumor microenvironment and response dynamics. To account for inter-tumor heterogeneity, it is necessary to apply a panel of models that are well characterized on a molecular biological level. With the right preclinical systems in place, combination strategies can be refined to optimize timing, dosing and sequencing of therapies to maximize tumor control while minimizing damage to normal tissues. Biomarker-driven approaches and molecular pathway analysis are increasingly guiding patient selection and therapeutic personalization, thereby improving the likelihood of clinical success. Examples include biomarker-based studies such as the DELPHI trial for dose de-escalation in post-op HPV-positive head and neck cancer (HNSCC) and the INDIRA Miso study on escalation of PET hypoxic HNSCC. Promising examples of novel combinations with radiotherapy include not only small molecule or Immunotherapeutics, but also the use of radiotherapy integration with novel theranostic radiopharmaceuticals, genomic and radiomic data for adaptive treatment planning. By aligning preclinical and clinical strategies, these efforts are advancing the integration of targeted therapies with radiotherapy and improve loco-regional control, overall survival and quality of life for patients. Citation Format: Michael Baumann. Moving forward translation of targeted therapy with external beam radiation. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA01

PFKFB3-dependent redox homeostasis and DNA repair support cell survival under EGFR-TKIs in non-small cell lung carcinoma

BackgroundThe efficacy of tyrosine kinase inhibitors (TKIs) targeting the EGFR is limited due to the persistence of drug-tolerant cell populations, leading to therapy resistance. Non-genetic mechanisms, such as metabolic rewiring, play a significant role in driving lung cancer cells into the drug-tolerant state, allowing them to persist under continuous drug treatment.MethodsOur study employed a comprehensive approach to examine the impact of the glycolytic regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3) on the adaptivity of lung cancer cells to EGFR TKI therapies. We conducted metabolomics to trace glucose rerouting in response to PFKFB3 inhibition during TKI treatment. Live cell imaging and DCFDA oxidation were used to quantify levels of oxidation stress. Immunocytochemistry and Neutral Comet assay were employed to evaluate DNA integrity in response to therapy-driven oxidative stress.ResultsOur metabolic profiling revealed that PFKFB3 inhibition significantly alters the metabolic profile of TKI-treated cells. It limited glucose utilization in the polyol pathway, glycolysis, and TCA cycle, leading to a depletion of ATP levels. Furthermore, pharmacological inhibition of PFKFB3 overcome TKI-driven redox capacity by diminishing the expression of glutathione peroxidase 4 (GPX4), thereby exacerbating oxidative stress. Our study also unveiled a novel role of PFKFB3 in DNA oxidation and damage by controlling the expression of DNA-glycosylases involved in base excision repair. Consequently, PFKFB3 inhibition improved the cytotoxicity of EGFR-TKIs by facilitating ROS-dependent cell death.ConclusionsOur results suggest that PFKFB3 inhibition reduces glucose utilization and DNA damage repair, limiting the adaptivity of the cells to therapy-driven oxidative stress and DNA integrity insults. Inhibiting PFKFB3 can be an effective strategy to eradicate cancer cells surviving under EGFR TKI therapy before they enter the drug-resistant state. These findings may have potential implications in the development of new therapies for drug-resistant cancer treatment.

An integral membrane constitutively active heparanase enhances the tumor infiltration capability of NK cells

ABSTRACT Eradication of cancer cells by the immune system requires extravasation, infiltration and progression of immune cells through the tumor extracellular matrix (ECM). These are also critical determinants for successful adoptive cell immunotherapy of solid tumors. Together with structural proteins, such as collagens and fibronectin, heparan sulfate (HS) proteoglycans are major components of the ECM. Heparanase 1 (HPSE) is the only enzyme known to have endoglycosidase activity that degrades HS. HPSE is expressed at high levels in almost all hematopoietic cells, which suggests that it plays a relevant role in immune cell migration through solid tissues. Besides, tumor cells express also HPSE as a way to facilitate tumor cell resettlement and metastasis. Therefore, an increase in HPSE in the tumor ECM would be detrimental. Here, we analyzed the effects of constitutive expression of an active, membrane-bound HPSE on the ability of human natural killer (NK) cells to infiltrate tumors and eliminate tumor cells. We demonstrate that NK cells expressing a chimeric active form of HPSE on the cell surface as an integral membrane protein, display significantly enhanced infiltration capability into spheroids of various cancer cell lines, as well as into xenograft tumors in immunodeficient mice. As a result, tumor growth was significantly suppressed without causing noticeable side effects. Altogether, our results suggest that a constitutively expressed active HSPE on the surface of immune effector cells enhances their capability to access and eliminate tumor cells. This strategy opens new possibilities for improving adoptive immune treatments using NK cells.

Development of Novel Imipridones with Alkyne- and Triazole-Linked Warheads on the Tricyclic Skeleton, Showing Superior Ability to Eradicate PANC-1 and Fadu Cells Compared to ONC201.

Our ongoing research focuses on the development of new imipridone derivatives. We aim to design compounds that can completely and selectively eradicate cancer cells after relatively short treatment. We have synthetized systematically designed novel hybrids and evaluated their antiproliferative activity against PANC-1 and Fadu cell lines. We have also conducted preliminary studies on the mechanism, including colony formation as well as dose-response tests in HEK293T wild-type (WT) and HEK293T CLPP-/- cells. Following gradual structural fine-tuning based on high throughput screening, we identified two imipridone hybrids as the most potent derivatives. Their unique substitution pattern includes N-methylated propargylamine and ferrocenyl/phenyltriazole moieties on the benzyl groups attached to opposite sides of the imipridone core. We found that the compounds with IC50 values similar to those of ONC201 completely eradicated cancer cells at about 4 μM, while ONC201 treatment at even higher concentrations left 30-50% of viable cells behind. Both compounds exerted equal activity in WT and CLPP-/- HEK293T cells, indicating a ClpP-independent mechanism. Further development is needed to improve the tumor selectivity of the two potent imipridone derivatives. By preserving tumor cytotoxicity, we aim to generate new drug candidates that evade resistance and can be applied in a sufficiently broad therapeutic window.

Cooperative tumor inhibition by CpG-oligodeoxynucleotide and cyclic dinucleotide in head and neck cancer involves T helper cytokine and macrophage phenotype reprogramming

Head and neck cancer ranks as the sixth most common cancer worldwide, highlighting the critical need for the development of new therapies to enhance treatment efficacy. The activation of innate immune receptors given their potent immune stimulatory properties aid in the eradication of cancer cells. In this study, we investigated the immune mechanism and anti-tumor function of a Toll-like receptor 9 (TLR9) agonist, CpG-oligodeoxynucleotide-2722 (CpG-2722), in combination with cyclic dinucleotides, which are agonists of stimulator of interferon genes (STING). Our results revealed that CpG-2722 stimulation increased the expression of Th1 pro-inflammatory cytokines. Stimulation by STING agonists exhibited lower expression of Th1 cytokines but higher expression of Th2 cytokines compared to CpG-2722. However, the combination of these two agonists significantly enhanced Th1 cytokines while reducing Th2 cytokines. Moreover, in vivo experiment showed that both CpG-2722 and 2'3'-c-di-AMP suppressed head and neck tumor growth, with their combination proving more effective than the use of these agonists alone. The combined treatment cooperatively promoted the production of Th1 cytokines and type I interferons, while suppressing Th2 cytokines in the tumors as observed in vitro. Additionally, it led to the accumulation of M1 macrophages, dendritic cells, and T cells, shaping a favorable tumor microenvironment for T cell-mediated tumor killing. The anti-tumor activity of the CpG-2722 and 2'3'-c-di-AMP combination depends on the macrophage presence but does not directly activate M1 macrophage polarization, instead working through a reprogrammed cytokine profile. Furthermore, this combination shows a cooperative anti-tumor activity with anti-PD-1 in treating head and neck tumors. Overall, these findings highlight a Th response and macrophage phenotype reprograming involved functional mechanism underlying the cooperative activity of the combination of TLR9 and STING agonists in the immunotherapy of head and neck cancer.

Mitochondrial transfer of drug-loaded artificial mitochondria for enhanced anti-Glioma therapy through synergistic apoptosis/ferroptosis/immunogenic cell death.

Mitochondrial targeting in gliomas represents a novel therapeutic strategy with significant potential to enhance drug sensitivity by effectively killing glioma cells at the mitochondrial level. In this study, we developed artificial mitochondria derived from mitochondrial membrane-based nanovesicles, enabling precise mitochondrial targeting of doxorubicin (Dox) to selectively eradicate cancer cells by amplifying multiple cell death pathways. It was found that Dox-encapsulating mitochondria-based nanovesicles (DOX-MitoNVs) exhibited an extraordinary ability to penetrate the blood-brain barrier (BBB), specifically targeting gliomas. By targeting mitochondria instead of locating at the nucleus, DOX-MitoNVs not only amplified Dox mediated apoptosis effects through the overloading of intracellular Ca2+ but also intensified ferroptosis by generating reactive oxygen species (ROS). Furthermore, DOX-MitoNVs demonstrated a significant ability to modulate the tumor immune microenvironment, thereby inducing pronounced immunogenic cell death (ICD) effects. In summary, it presents a novel therapeutic strategy utilizing DOX-MitoNVs for precise mitochondrial targeting in gliomas, enhancing drug sensitivity, inducing multiple cell death pathways, and modulating the tumor immune microenvironment to promote immunogenic cell death. STATEMENT OF SIGNIFICANCE: Mitochondrial targeting in gliomas is a promising therapeutic strategy that enhances drug sensitivity by exploiting glioma cells' mitochondrial vulnerabilities. We engineered mitochondrial membrane-based nanovesicles as artificial mitochondria for precise mitochondrial targeting of Dox. This approach facilitates selective cancer cell eradication and amplifies multiple cell death pathways alongside immunogenic chemotherapy. Notably, DOX-MitoNVs effectively cross the BBB and specifically target gliomas. By focusing on mitochondria, Dox induces apoptosis and intensifies ferroptosis through ROS generation. Additionally, DOX-MitoNVs can transform the tumor immune microenvironment, promoting ICD. Overall, DOX-MitoNVs offer a promising platform for enhanced glioma therapy.

Identification of tanshinone I as a natural Cu(II) ionophore

The development of Cu(II) ionophores for targeted disruption of aberrant redox homeostasis in cancer cells has been considered an appealing strategy in the field of anticancer research. This study presents the first identification of tanshinone I (Ts1), a natural o-quinone, as a Cu(II) ionophore. Structure-activity relationship studies on tanshinones and mechanistic investigations reveal that the presence of Cu(II) effectively promotes the tautomerization of Ts1 from its diketo to keto-enol forms, thereby facilitating its sequential proton-loss Cu(II) chelation, and enabling it to function as a Cu(II) ionophore due to its structural features including the presence of an o-quinone moiety, a benzyl hydrogen, and a large conjugated system. The unique property allows Ts1 to preferentially induce copper accumulation in human hepatoma HepG2 cells over human umbilical vein endothelial cells, by releasing copper driven by reduced glutathione (GSH). This copper accumulation leads to a reduction in the GSH-to-oxidized glutathione ratio and the generation of reactive oxygen species, ultimately triggering apoptosis of HepG2 cells. The findings not only provide support for o-quinones as innovative types of anticancer Cu(II) ionophores, but also shed light on the previously unrecognized role of Ts1 as a potent Cu(II) ionophore for eradicating cancer cells by selectively disrupting their redox regulation programs, resembling a "Trojan horse".

UV radiation enhanced encapsulation of superparamagnetic iron oxide nanoparticles (MNPs) in microparticles derived from tumor repopulating cells

Extracellular vesicles (EVs) such as microparticles secreted by the cells can be manipulated and used for delivering therapeutic drugs to target and eradicate cancer cells. However, high encapsulation efficiency and mass production of the microparticles remain difficult to achieve. Efficient and targeted delivery to cancer cells is another hurdle to be addressed. To overcome these issues, we integrated superparamagnetic iron oxide nanoparticles (MNPs) with microparticles. First of all, exposure of highly aggressive tumor-repopulating cells (TRC) to UV radiation dramatically improved microparticle production. These TRC cells were selected from diverse cancer cell lines that are 3D culturing in soft fibrin gel. These microparticles derived from 3D-cultured TRCs have lower membrane stiffness than 2D-cultured cells. Ferrozine assay showed that endocytosis and encapsulation of MNPs during microparticle production were higher in 3D-cultured TRC cells than in 2D cultured cells. Packaging of MNPs into microparticles also enhanced cellular uptake of MNPs without inducing cytotoxicity to treated cells. Compared to the naked MNPs, ex vivo fluorescence imaging shows that mice tail-vein injected with microparticle-encapsulated MNPs displayed continuous increments of intratumoral accumulation of MNPs. Furthermore, MRI images revealed a higher T2 contrast and an uneven distribution of the T2 contrast in the tumor of mice tail-vein injected with microparticle-encapsulated MNPs than naked MNPs. This study provides a new platform for cancer imaging by integrating MNPs and microparticles derived from tumor-repopulating cells.

Combination therapy of Lapatinib/Letrozole-based protein-vitamin nanoparticles to enhance the therapeutic effectiveness in drug-resistant breast cancer

HER2-positive breast cancer constitutes 20% of reported cases, characterized by excessive expression of HER2 receptors, pivotal in cell signaling and growth. Immunotherapy, the established treatment, often leads to multidrug resistance and tumor recurrence. There's a critical need for an effective strategy delaying drug resistance onset and ensuring cancer cell eradication. This study aimed to develop nanoparticles using human serum albumin (HSA) coupled with vitamin E (α-tocopherol succinate), loaded with a tyrosine kinase inhibitor (TKI) or aromatase inhibitor (AI). Nanoparticles were formed via desolvation, where HSA(VE) conjugates self-organized into a nanoparticle structure, incorporating TKI/AI either through chemical conjugation or direct binding to HSA. Physico-chemical analyses—such as infrared spectroscopy (IR), gel permeation chromatography (GPC), UV, IR, and CD spectroscopy confirmed HSA(VE) binding and drug incorporation into nanoparticles, evaluating their drug entrapment, release efficiency. Cell viability assays and in-vitro experiments on resistant and sensitive cell lines demonstrated effective drug encapsulation and absorption over time. Both in vitro and in vivo studies demonstrated that a combination of Lapa@HSA(VE) NPs and Let@HSA(VE) NPs in the ratio 75:25 inhibited tumor development and enhanced apoptosis significantly compared to individual NP treatment and free drug. The combination NPs therapy exhibited significant efficacy even in Lapa-resistant cell lines.

Multifunctional iron-doped carbon dots: Integration of fluorescence and magnetic resonance imaging for enhanced photodynamic therapy

Multidimensional imaging materials are highly sought after in scientific research and clinical applications due to their ability to provide comprehensive imaging data while minimizing experimental interference. The iron-doped carbon dots (TPFe-CDs) prepared in this study possess dual-mode imaging capabilities, combining fluorescence and magnetic resonance imaging, along with photodynamic therapy functionality. In fluorescence imaging, TPFe-CDs exhibit versatility, being effectively excited by either single-photon or two-photon excitation. This versatility enables successful imaging across various biological samples, including cells, organoids, and zebrafish. Moreover, TPFe-CDs demonstrate exceptional three-dimensional imaging capabilities, penetrating depths exceeding 300 µm, thus enabling deeper tissue imaging beyond surface layers. Additionally, TPFe-CDs serve as excellent contrast agents in magnetic resonance imaging, showcasing a T2 relaxation rate of 10.388 mM−1s−1. In mouse models, magnetic resonance imaging revealed potential targeting of TPFe-CDs, primarily accumulating in the thoracic lung region, with minimal distribution observed in the gastrointestinal tract and tail regions. Furthermore, TPFe-CDs exhibit promising photodynamic therapy capabilities, generating reactive oxygen species (ROS) upon laser irradiation, leading to successful cancer cell eradication in experimental settings. The multifunctional nature of TPFe-CDs, with their dual-modal imaging capabilities and therapeutic potential, is garnering significant attention and is poised to make substantial contributions to diverse fields such as biological imaging and clinical therapy.

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.

Tubulin-Targeted Therapy in Melanoma Increases the Cell Migration Potential by Activation of the Actomyosin Cytoskeleton─An In Vitro Study.

One of the most dangerous aspects of cancers is their ability to metastasize, which is the leading cause of death. Hence, it holds significance to develop therapies targeting the eradication of cancer cells in parallel, inhibiting metastases in cells surviving the applied therapy. Here, we focused on two melanoma cell lines─WM35 and WM266-4─representing the less and more invasive melanomas. We investigated the mechanisms of cellular processes regulating the activation of actomyosin as an effect of colchicine treatment. Additionally, we investigated the biophysical aspects of supplement therapy using Rho-associated protein kinase (ROCK) inhibitor (Y-27632) and myosin II inhibitor ((-)-blebbistatin), focusing on the microtubules and actin filaments. We analyzed their effect on the proliferation, migration, and invasiveness of melanoma cells, supported by studies on cytoskeletal architecture using confocal fluorescence microscopy and nanomechanics using atomic force microscopy (AFM) and microconstriction channels. Our results showed that colchicine inhibits the migration of most melanoma cells, while for a small cell population, it paradoxically increases their migration and invasiveness. These changes are also accompanied by the formation of stress fibers, compensating for the loss of microtubules. Simultaneous administration of selected agents led to the inhibition of this compensatory effect. Collectively, our results highlighted that colchicine led to actomyosin activation and increased the level of cancer cell invasiveness. We emphasized that a cellular pathway of Rho-ROCK-dependent actomyosin contraction is responsible for the increased invasive potential of melanoma cells in tubulin-targeted therapy.

In silico and in vitro evaluation of a PE38 and Nb-based recombinant immunotoxin targeting the GRP78 receptor in cancer cells.

Cancer is a global health problem despite the most developed therapeutic modalities. The delivery of specific therapeutic agents to a target increases the effectiveness of cancer treatment by reducing side effects and post-treatment issues. Our aim in this study was to design a recombinant protein consisting of nanobody molecules and exotoxin that targets the surface GRP78 receptor on tumor cells. Bioinformatics methods make drug design and recombinant protein evaluation much easier before the laboratory steps. Two constructs were designed from a single-variable domain on heavy chain nanobody domains and PE toxin domains II, Ib, and III. The physicochemical properties, secondary structure, and solubility of the chimeric protein were analyzed using different software. Prostate cancer DU-145 and breast cancer MDA-MB-468 cell lines were used as GRP78-positive and negative controls, respectively. Accordingly, the cytotoxicity, binding affinity, cell internalization, and apoptosis were evaluated using MTT, enzyme-linked immunosorbent assay, and western blot. The results showed that in the DU-145 cell line, the cytotoxicity of two recombinant immunotoxins is dose and time-dependent. In MDA-MB-468 and HEK-293 cells, such an event does not occur. It is possible that two constructs designed for immunotoxins can attach to GRP78-positive cancer cells and then eradicate cancer cells by internalization and apoptosis. As our in vitro results were in line with in silico data confirming the Bioinformatics predictions, it can be concluded that the designed recombinant immunotoxins may exhibit therapeutic potential against GRP78-positive tumor cells.

Divergent Syntheses of Near-Infrared Light-Activated Molecular Jackhammers for Cancer Cell Eradication.

Aminocyanines incorporating Cy7 and Cy7.5 moieties function as molecular jackhammers (MJH) through vibronic-driven action (VDA). This mechanism, which couples molecular vibrational and electronic modes, results in picosecond-scale concerted stretching of the entire molecule. When cell-associated and activated by near-infrared light, MJH mechanically disrupts cell membranes, causing rapid necrotic cell death. Unlike photodynamic and photothermal therapies, the ultrafast vibrational action of MJH is unhindered by high concentrations of reactive oxygen species scavengers and induces only a minimal temperature increase. Here, the efficient synthesis of a library of MJH is described using a practical approach to access a key intermediate and facilitating the preparation of various Cy7 and Cy7.5 MJH with diverse side chains in moderate to high yields. Photophysical characterization reveals that structural modifications significantly affect molar extinction coefficients and quantum yields while maintaining desirable absorption and emission wavelengths. The most promising compounds, featuring dimethylaminoethyl and dimethylcarbamoyl substitutions, demonstrate up to sevenfold improvement in phototherapeutic index compared to Cy7.5 amine across multiple cancer cell lines. This synthetic strategy provides a valuable platform for developing potent, light-activated therapeutic agents for cancer treatment, with potentially broad applicability across various cancer types.

Multi-Enzyme Nanoparticles as Efficient Pyroptosis and Immunogenic Cell Death Inducers for Cancer Immunotherapy.

Immunotherapy represents a widely employed modality in clinical oncology, leveraging the activation of the human immune system to target and eradicate cancer cells and tumor tissues via endogenous immune mechanisms. However, its efficacy remains constrained by inadequate immune responses within "cold" tumor microenvironment (TME). In this study, a multifunctional nanoscale pyroptosis inducer with cascade enzymatic activity (IMZF), comprising superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and glutathione oxidase (GSHOx), is dissociated within the acidic and glutathione-rich TME. The vigorous enzymatic activity not only generates oxygen (O2) to alleviate hypoxia and promote M2 to M1 macrophage polarization but also yields reactive oxygen species (ROS) and depletes glutathione (GSH) within the TME. Functioning as an immunogenic cell death (ICD) activator and pyroptosis inducer, IMZF synergistically triggers dendritic cell maturation and inflammatory lymphocyte infiltration via ICD-associated pyroptosis, thereby reversing immune suppression within the TMEs. Consequently, it exerts inhibitory effects on both primary and distal tumors. This cascade enzymatic platform-based pyroptosis inducer offers an intelligent strategy for effectively overcoming immune suppression within "cold" tumors, thereby providing a promising avenue for advanced immunotherapeutic interventions.

CD8+ T cell associated scoring model helps prognostic diagnosis and immunotherapy selection in patients with colon adenocarcinoma

ObjectiveT cell-mediated immunity plays a crucial role in the immune response against tumors, with CD 8+ T cells playing a leading role in the eradication of cancer cells. Material and methodsA total of 5 datasets were included in this study. Single cell transcriptome data were used to discover CD8+ T cell marker genes, and Bulk transcriptome data from TCGA and GEO were jointly analyzed to screen candidate prognostic genes. lasso regression was performed to construct prognostic models. Immunotherapy cohort (IMvigor 210 and GSE78220) was applied to validate the diagnostic power of markers. ResultSingle-cell transcriptome data identified 65 CD8+ T cell marker genes, highlighting their importance in T cell-mediated immune responses. Among these, 11 genes were identified as CD8+ T-associated differential genes through analysis of bulk data from TCGA and GEO. A prognostic model for 5 genes was identified based on Lasso regression, dividing colon adenocarcinoma (COAD) patients into high- and low-risk groups. This model exhibited higher prognostic accuracy compared to traditional clinicopathological characteristics (age, pathological stage, histological grading). Moreover, the risk score derived from this model successfully differentiated patient responses to immunotherapy, as validated in the IMvigor 210 and GSE78220 cohorts. ConclusionOur research introduces a novel prognostic signature based on CD8+ T cell marker genes, demonstrating significant predictive power for prognosis and immunotherapy response in COAD patients. This model offers a potential tool for improving patient stratification and personalizing treatment strategies.

Applications and challenges of photodynamic therapy in the treatment of skin malignancies.

Photodynamic Therapy (PDT), as a minimally invasive treatment method, has demonstrated its distinct advantages in the management of skin malignant tumors. This article examines the current application status of PDT, assesses its successful cases and challenges in clinical treatment, and anticipates its future development trends. PDT utilizes photosensitizers to interact with light of specific wavelengths to generate reactive oxygen species that selectively eradicate cancer cells. Despite PDT's exceptional performance in enhancing patients' quality of life and prognosis, the limitation of treatment depth and the side effects of photosensitizers remain unresolved issues. With the advancement of novel photosensitizers and innovative treatment technology, the application prospects of PDT are increasingly expansive. This article delves into the mechanism of PDT, its application in various skin malignancies, its advantages and limitations, and envisions its future development. We believe that through continuous technological enhancements and integration with other treatment technologies, PDT has the potential to assume a more pivotal role in the treatment of skin malignancies.

Nanoengineered Injectable Hydrogel: An Advanced Radioprotective Barrier with Magnetic Hyperthermia Synergy.

Despite its effectiveness in eradicating cancer cells, current tumor radiotherapy often causes irreversible damage to the surrounding healthy tissues. To address this issue and enhance therapeutic outcomes, we developed a multifunctional injectable hydrogel that integrates electromagnetic shielding and magnetothermal effects. This innovation aims to improve the efficacy of brachytherapy while protecting adjacent normal tissues. Recognizing the limitations of existing hydrogel materials in terms of stretchability, durability, and single functionality, we engineered a composite hydrogel by self-assembling nickel nanoparticles on the surface of liquid metal particles and embedding them into an injectable hydrogel matrix. The resulting composite material demonstrates superior electromagnetic interference shielding performance (74.89 dB) and a rapid magnetothermal heating rate (10.9 °C/min), significantly enhancing its in vivo applicability. The experimental results confirm that this innovative nanocomposite hydrogel effectively attenuates electromagnetic waves during brachytherapy, thereby protecting normal tissues surrounding the tumor and enhancing radiotherapy efficacy through magnetothermal therapy. This study advances the safety and effectiveness of cancer treatments and provides new insights into the development of multifunctional biomedical materials, promoting the innovative application of nanotechnology in the medical field.

Novel platinum therapeutics induce rapid cancer cell death through triggering intracellular ROS storm

Induction of reactive oxygen species (ROS) production in cancer cells plays a critical role for cancer treatment. However, therapeutic efficiency remains challenging due to insufficient ROS production of current ROS inducers. We designed a novel platinum (Pt)-based drug named “carrier-platin” that integrates ultrasmall Pt-based nanoparticles uniformly confined within a poly(amino acids) carrier. Carrier-platin dramatically triggered a burst of ROS in cancer cells, leading to cancer cell death as quick as 30 min. Unlike traditional Pt-based drugs which induce cell apoptosis through DNA intercalation, carrier-platin with superior ROS catalytic activities induces a unique pattern of cancer cell death that is neither apoptosis nor ferroptosis and operates independently of DNA damage. Importantly, carrier-platin demonstrates superior anti-tumor efficacy against a broad spectrum of cancers, particularly those with multidrug resistance, while maintaining minimal systemic toxicity. Our findings reveal a distinct mechanism of action of Pt in cancer cell eradication, positioning carrier-platin as a novel category of anti-cancer chemotherapeutics.