Kill Cancer Cells Research Articles

MTA-Cooperative PRMT5 Inhibitors: Mechanism Switching Through Structure-Based Design.

Deletion of the MTAP gene leads to accumulation of the substrate of the MTAP protein, methylthioadenosine (MTA). MTA binds PRMT5 competitively with S-adenosyl-l-methionine (SAM), and selective inhibition of the PRMT5•MTA complex relative to the PRMT5•SAM complex can lead to selective killing of cancer cells with MTAP deletion. Herein, we describe the discovery of novel compounds using structure-based drug design to switch the mechanism of binding of known, SAM-cooperative PRMT5 inhibitors to an MTA-cooperative binding mechanism by occupying the portion of the SAM binding pocket in PRMT5 that is unoccupied when MTA is bound and hydrogen bonding to Arg368, thereby allowing them to selectively target MTAP-deleted cancer cells.

DNA Logic Gate-Triggered Membrane Fusion for Accurately Detecting and Killing Cancer Cells.

Accurately and sensitively identifying and killing cancer cells, especially those in deep tissues, is of paramount importance but presents significant challenges. Herein, a membrane protein and adenosine triphosphate (ATP)-driven DNA logic gate-modified liposome is designed to coat zinc peroxide (ZP) nanoparticles integrated with nanozymes (ZP/RuTe@L/DNA) to accurately identify and induce cell apoptosis in cancer cells through a reactive oxygen species (ROS)-mediated mechanism under acid conditions in cancer cells. In this system, DNA logic gate-functionalized liposomes are loaded with ZP and nanozymes, while HeLa cancer cells are functionalized with a DNA segment that is complementary to a segment of the DNA logic gate. For the DNA logic gate, a DNA aptamer was employed for membrane protein recognition, and another aptamer was used for the response of extracellular ATP. Activation of the DNA logic gate occurs only when both biomarkers are simultaneously present. Once activated, the DNA logic gate-modified liposome could hybridize with DNA segment-modified HeLa cells, leading to liposome-HeLa cell fusion and the release of ZP/RuTe into HeLa cells. Under acid conditions, ZP could decompose to release H2O2 and Zn2+, which could promote the production of •O2- and H2O2 by inhibiting the electron transport chain. Concurrently, the released RuTe exhibits glutathione (GSH) depletion and peroxidase (POD) and nicotinamide adenine dinucleotide (NADH) peroxidase-like activities, generating highly toxic hydroxyl radical (•OH), disrupting the cellular redox homeostasis, and inducing cell apoptosis. The ZP/RuTe@L/DNA system could not only accurately detect cancer cells in complex cell mixtures but also present a novel method for liposome-membrane fusion processes in drug delivery. This study presents significant potential for application in precise cancer diagnosis and therapy.

Cancer stem cell populations are resistant to 5-aminolevulinic acid-photodynamic therapy (5-ALA-PDT)

Photodynamic therapy (PDT) is a minimally invasive treatment approved for many types of cancers. PDT involves the administration of photoactive substances called photosensitizers (PS) that selectively accumulate in cancer cells and are subsequently excited/activated by irradiation with light at wavelengths of optimal absorbance. Activated PS leads to the generation of singlet oxygen and other reactive oxygen species (ROS), promoting cancer cell death. 5-aminolevulinic acid (5-ALA) is a naturally occurring PS precursor, which is metabolically converted to the PS, protoporphyrin IX (PPIX). Although 5-ALA-PDT is effective at killing cancer cells, in prior studies conducted by our group we normally observed in in vitro experiments that approximately 5–10% of cells survive 5-ALA-PDT, which served as an impetus for further investigation. Identifying the mechanisms of resistance to 5-ALA-PDT-mediated cell death is important to prevent tumor recurrence following 5-ALA-PDT. Previously, we reported that oncogenic activation of Ras/MEK promotes PPIX efflux and reduces cellular sensitivity to 5-ALA-PDT through increased expression of ABCB1 transporter. As cancer stem cells (CSCs) are known to drive resistance to other cancer treatments and have high efflux of chemotherapeutic agents via ABC-family transporters, we hypothesize that CSCs underlie 5-ALA-PDT resistance. In this study, we determined (1) if CSCs are resistant to 5-ALA-PDT and (2) if CSCs play roles in establishing resistant populations of 5-ALA-PDT. When we compared CSC populations before and after 5-ALA-PDT, we found that CSCs were less susceptible to 5-ALA-PDT. Moreover, we found that the CSC population was enriched in 5-ALA-PDT-resistant cell lines compared to the parental cell line. Our results indicate that CSCs are not sensitive to 5-ALA-PDT, which may contribute to establishment of 5-ALA-PDT resistance.

Glucuronidase-Instructed Glycopeptide Self-Assembly for Selective Killing of Cancer Cells through Lysosomal Membrane Permeabilization.

Current cancer treatments face significant challenges, including limited tumor specificity and drug resistance. Enzyme-instructed supramolecular peptide assembly targeting lysosomes offers a promising strategy to address these issues; however, self-assembling units that withstand lysosomal conditions are still scarce. In this study, we present a versatile glycopeptide incorporating glucuronic acid and glucose that undergoes glucuronidase-triggered self-assembly to form nanofibers, leading to lysosomal membrane permeabilization (LMP) in cancer cells. Mechanistic studies revealed that in glucuronidase-overexpressing HepG2 cells, glycopeptide assembly induces cytoskeletal disruption and apoptosis. The involvement of carbohydrate-binding receptor in enhancing the cellular entry of glycopeptides and improving proteolytic stability highlights the importance of glycan modification. Notably, combining this glycopeptide with cisplatin or adriamycin results in synergistic cytotoxicity, including in drug-resistant cancer lines. These findings establish a novel, LMP-inducing glycopeptide scaffold for developing targeted approaches for cancer treatment.

Glucuronidase‐Instructed Glycopeptide Self‐Assembly for Selective Killing of Cancer Cells through Lysosomal Membrane Permeabilization

Glucuronidase‐Instructed Glycopeptide Self‐Assembly for Selective Killing of Cancer Cells through Lysosomal Membrane Permeabilization

Breaking barriers: Smart vaccine platforms for cancer immunomodulation.

Despite significant advancements in cancer treatment, current therapies often fail to completely eradicate malignant cells. This shortfall underscores the urgent need to explore alternative approaches such as cancer vaccines. Leveraging the immune system's natural ability to target and kill cancer cells holds great therapeutic potential. However, the development of cancer vaccines is hindered by several challenges, including low stability, inadequate immune response activation, and the immunosuppressive tumor microenvironment, which limit their efficacy. Recent progress in various fields, such as click chemistry, nanotechnology, exosome engineering, and neoantigen design, offer innovative solutions to these challenges. These achievements have led to the emergence of smart vaccine platforms (SVPs), which integrate protective carriers for messenger ribonucleic acid (mRNA) with functionalization strategies to optimize targeted delivery. Click chemistry further enhances SVP performance by improving the encapsulation of mRNA antigens and facilitating their precise delivery to target cells. This review highlights the latest developments in SVP technologies for cancer therapy, exploring both their opportunities and challenges in advancing these transformative approaches.

Metformin Induces Apoptosis and Ferroptosis of Ovarian Cancer Cells Under Energy Stress Conditions

As ovarian cancer progresses, increased glucose use causes a glucose shortage in the tumor microenvironment. Therefore, it is crucial to find drugs that can effectively kill cancer cells in this energy stress setting. Here, we propose an effective therapeutic strategy that combines nutrient restriction with metformin to combat tumors. This study investigated the effects of metformin on ovarian cancer cells under energy stress conditions, mimicking the nutrient-deprived tumor microenvironment. We revealed that Metformin (10 mM) significantly reduced cell viability and proliferation under glucose deprivation conditions. Furthermore, it enhanced apoptosis and ferroptosis, as demonstrated by alterations in apoptotic protein expression and elevated levels of lipid reactive oxygen species (ROS), malondialdehyde (MDA), lipid peroxidation (LPO), and Fe2+. Transcriptional profiling revealed significant alterations in genes related to iron homeostasis and oxidative phosphorylation. Moreover, Metformin was found to induce mitochondrial dysfunction without affecting mitochondrial DNA or the expression of enzymes in the tricarboxylic acid (TCA) cycle, resulting in decreased ATP production and compromised activities of the respiratory chain complexes. The direct interaction between metformin and the NDUFB4 subunit in mitochondrial complex I was corroborated through the application of cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) assays. In vivo, the combination of metformin and fasting cycles significantly inhibited SKOV3 cell-derived xenograft tumors in immunodeficient mice. Altogether, we have demonstrated that Metformin potentiates apoptosis and ferroptosis in ovarian cancer cells under energy stress conditions by targeting the NDUFB4 subunit of mitochondrial complex I, thus laying the groundwork for clinical testing. This study, though limited to cellular and animal levels, provides valuable insights into the therapeutic potential of metformin in ovarian cancer treatment.

Discovery of anticancer peptides from natural and generated sequences using deep learning.

Anticancer peptides (ACPs) demonstrate significant potential in clinical cancer treatment due to their ability to selectively target and kill cancer cells. In recent years, numerous artificial intelligence (AI) algorithms have been developed. However, many predictive methods lack sufficient wet lab validation, thereby constraining the progress of models and impeding the discovery of novel ACPs. This study proposes a comprehensive research strategy by introducing CNBT-ACPred, an ACP prediction model based on a three-channel deep learning architecture, supported by extensive in vitro and in vivo experiments. CNBT-ACPred achieved an accuracy of 0.9554 and a Matthews Correlation Coefficient (MCC) of 0.8602. Compared to existing excellent models, CNBT-ACPred increased accuracy by at least 5% and improved MCC by 15%. Predictions were conducted on over 3.8 million sequences from Uniprot, along with 100,000 sequences generated by a deep generative model, ultimately identifying 37 out of 41 candidate peptides from >30 species that exhibited effective in vitro tumor inhibitory activity. Among these, tPep14 demonstrated significant anticancer effects in two mouse xenograft models without detectable toxicity. Finally, the study revealed correlations between the amino acid composition, structure, and function of the identified ACP candidates.

Managing Doxorubicin Cardiotoxicity: Insights Into Molecular Mechanisms and Protective Strategies.

Cancer ranks as the second leading cause of death in the United States and poses a significant health challenge globally. Numerous therapeutic options exist for treating cancer, with chemotherapy being one of the most prominent. Chemotherapy involves the use of antineoplastic drugs, either alone or in combination with other medications, to target and kill cancer cells. However, these drugs can also adversely affect healthy cells, leading to various side effects. Among the most commonly used chemotherapy agents are anthracyclines, which include doxorubicin, daunorubicin, and epirubicin. Doxorubicin is particularly notable for its effectiveness but is also associated with significant cardiotoxicity, a common concern for patients undergoing chemotherapy. Unfortunately, there is currently no definitive treatment to prevent or reverse this cardiotoxicity. The cardiac effects of doxorubicin can manifest in several ways, including changes in electrocardiograms, arrhythmias, myocarditis, pericarditis, myocardial infarction, cardiomyopathy, heart failure, and congestive heart failure. These complications may arise during treatment, shortly after it concludes, or even weeks later. Various mechanisms have been proposed to explain doxorubicin-induced cardiotoxicity. Key factors include the inhibition of topoisomerase IIβ, mitochondrial damage, reactive oxygen species (ROS) production due to iron metabolism, increased oxidative stress, heightened inflammatory responses, and elevated rates of apoptosis and necrosis within cardiac tissue. This review article will provide a comprehensive overview of the current state of knowledge regarding doxorubicin-induced cardiomyopathy. We will explore the underlying molecular mechanisms contributing to this condition and discuss emerging therapeutic strategies aimed at mitigating its impact on cancer survivors.

Bioengineering stimuli-responsive organic-inorganic nanoarchitetures based on carboxymethylcellulose-poly-l-lysine nanoplexes: Unlocking the potential for bioimaging and multimodal chemodynamic-magnetothermal therapy of brain cancer cells.

Regrettably, glioblastoma multiforme (GBM) remains the deadliest form of brain cancer, where the early diagnosis plays a pivotal role in the patient's therapy and prognosis. Hence, we report for the first time the design, synthesis, and characterization of new hybrid organic-inorganic stimuli-responsive nanoplexes (NPX) for bioimaging and killing brain cancer cells (GBM, U-87). These nanoplexes were built through coupling two nanoconjugates, produced using a facile, sustainable, green aqueous colloidal process ("bottom-up"). One nanocomponent was based on cationic epsilon-poly-l-lysine polypeptide (εPL) conjugated with ZnS quantum dots (QDs) acting as chemical ligand and cell-penetrating peptide (CPP) for bioimaging of cancer cells (QD@εPL). The second nanocomponent was based on anionic carboxymethylcellulose (CMC) polysaccharide surrounding superparamagnetic magnetite "nanozymes" (MNZ) behaving as a capping macromolecular shell (MNZ@CMC) for killing cancer cells through chemodynamic therapy (CDT) and magnetohyperthermia (MHT). The results demonstrated the effective production of supramolecular aqueous colloidal nanoplexes (QD@εPL_MNZ@CMC, NPX) integrated into single nanoplatforms, mainly electrostatically stabilized by εPL/CMC biomolecules with anticancer activity against U-87 cells using 2D and 3D spheroid models. They displayed nanotheranostics (i.e., diagnosis and therapy) behavior credited to the photonic activity of QD@εPL with luminescent intracellular bioimaging, amalgamated with a dual-mode killing effect of GBM cancer cells through CDT by nanozyme-induced biocatalysis and as "nanoheaters" by magnetically-responsive hyperthermia therapy.

Promoting macrophage phagocytosis of cancer cells for effective cancer immunotherapy.

Cancer therapy has been revolutionized by immunotherapeutic agents exploiting adaptive antitumor immunity in the past two decades. However, the overall response rate of these immunotherapies is limited, and patients also develop resistance upon treatment, promoting a rapidly growing exploration of anti-tumor innate immunity for effective cancer therapy. Among these, macrophage immunotherapy through harnessing macrophage phagocytosis has been thrust into the spotlight due to its potential for simultaneously inducing cancer cell killing effect and mobilizing adaptive antitumor responses. Here in this review, we summarize the current macrophage immunotherapy such as therapeutic antibodies, phagocytosis checkpoint blockades, and CAR-macrophages with a particular emphasis on the resistant mechanisms limiting their therapeutic effects. Moreover, we further survey the efforts being placed to seek synergistic mechanisms and combination strategies for promoting macrophage phagocytosis which might stand as next-generation cancer immunotherapy.

Identification of TTLL8, POTEE, and PKMYT1 as immunogenic cancer-associated antigens and potential immunotherapy targets in ovarian cancer

ABSTRACT Most high-grade serous ovarian cancers (OC) do not respond to current immunotherapies. To identify potential new actionable tumor antigens in OC, we performed immunopeptidomics on a human OC cell line expressing the HLA-A02:01 haplotype, which is commonly expressed across many racial and ethnic groups. From this dataset, we identified TTLL8, POTEE, and PKMYT1 peptides as candidate tumor antigens with low expression in normal tissues and upregulated expression in OC. Using tissue microarrays, we assessed the protein expression of TTLL8 and POTEE and their association with patient outcomes in a large cohort of OC patients. TTLL8 was found to be expressed in 56.7% of OC and was associated with a worse overall prognosis. POTEE was expressed in 97.2% of OC patients and had no significant association with survival. In patient TILs, increases in cytokine production and tetramer-positive populations identified antigen-specific CD8 T cell responses, which were dependent on antigen presentation by HLA class I. Antigen-specific T cells triggered cancer cell killing of antigen-pulsed OC cells. These findings suggest that TTLL8, POTEE, and PKMYT1 are potential targets for the development of antigen-targeted immunotherapy in OC.

Nanoscale Ligand Spacing Regulates Mechanical Force-Induced Cancer Cell Killing.

Cancer cells sense and respond to the extracellular environment, with differences in nanoscale ligand spacing affecting their behavior. Emerging reports show that stretch/ultrasound-mediated mechanical forces promote apoptosis (mechanoptosis) by increasing myosin contractility. Since myosin contractility is critical for nanoscale-ligand spacing-regulated cell behavior, we study the effect of ligand spacing on mechanoptosis. Gold nanoparticle arrays were created with 35, 50, and 70 nm spacings and functionalized with cyclic-RGD peptide. Interestingly, the highest level of apoptosis was observed on 50 and 70 nm ligand spacing, where increased myosin contractility and peripheral Piezo1 channel localization causing calcium influx were observed. Perturbing cell-matrix interactions by nanomolar doses of Cilengitide (cyclic RGD pentapeptide) increases mechanoptosis on 35 nm ligand spacing to similar levels observed on 50 and 70 nm. Thus, nanoscale-level changes in binding domains regulate mechanoptosis through cell-matrix mediated mechanotransduction, and the synergistic action of ultrasound and Cilengitide can ultimately be applied to enhance tumor treatment.

Structural characterization and immunomodulatory activity of polysaccharides from the flowers of Imperata cylindrica Beauv.var. major (Nees) C.E.Hubb

BackgroundPolysaccharides are the main active components of Imperata cylindrica; however, research primarily targets its roots, with limited studies on flower-derived polysaccharides.ResultsTwo polysaccharides, FIC-1 and FIC-2, were extracted from the flowers of Imperata cylindrica using water extraction and ethanol precipitation. They were characterized by FT-IR, HPGPC, and SEM, with FIC-1 undergoing additional methylation and NMR analysis. FIC-1 was a neutral polysaccharide with a molecular weight of 5.3 kDa, while FIC-2 was an acidic polysaccharide with a molecular weight of 23.3 kDa. The two polysaccharides had distinct surface morphologies: FIC-1 had a rough, flocculent structure, while FIC-2 was smooth and lamellar. FIC-1’s main chain consists of →4)-β-D-Glcp-(1→, α-D-Glcp-(1→, →3)-β-D-Galp-(1→, →5)-α-L-Araf-(1→, and →4,6)-α-D-Manp-(1→ linkages, with side chains mainly formed by α-L-Araf-(1→ linked at the O-4 position of →4,6)-α-D-Manp-(1→. Further analysis of FIC-1 indicated that it promoted M1 macrophage polarization, activated NF-κB signaling pathway, and enhanced glycolysis and phagocytosis. While FIC-1 did not directly kill cancer cells, the cytokine-rich medium from FIC-1-stimulated macrophages significantly inhibited the proliferation of LLC1, ID8, and Hepa1-6 cancer cells.ConclusionsThese findings provide useful evidence that support the development and potential clinical application of polysaccharides derived from the flowers of Imperata cylindrica.Graphical

Fluorescent Neutron Track Detectors for Boron-10 Microdistribution Measurement in BNCT: A Feasibility Study

Boron Neutron-Capture Therapy (BNCT) is a form of radiation therapy that relies on the highly localized and enhanced biological effects of the 10B neutron capture (BNC) reaction products to selectively kill cancer cells. The efficacy of BNCT is, therefore, strongly dependent on the 10B spatial microdistribution at a subcellular level. Fluorescent Nuclear Track Detectors (FNTDs) could be a promising technology for measuring 10B microdistribution. They allow the measurement of the tracks of charged particles, and their biocompatibility allows cell samples to be deposited and grown on their surfaces. If a layer of borated cells is deposited and irradiated by a neutron field, the energy deposited by the BNC products and their trajectories can be measured by analyzing the corresponding tracks. This allows the reconstruction of the position where the measured particles were generated, hence the microdistribution of 10B. With respect to other techniques developed to measure 10B microdistribution, FNTDs would be a non-destructive, biocompatible, relatively easy-to-use, and accessible method, allowing the simultaneous measurement of the 10B microdistribution, the LET of particles, and the evolution of the related biological response on the very same cell sample. An FNTD was tested in three irradiation conditions to study the feasibility of FNTDs for BNCT applications. The FNTD allowed the successful measurement of the correct alpha particle range and mean penetration depth expected for all the radiation fields employed. This work proved the feasibility of FNTD in reconstructing the tracks of the alpha particles produced in typical BNCT conditions, thus the 10B microdistribution. Further experiments are planned at the University of Pavia’s LENA (Applied Nuclear Energy Laboratory) to test the final set-up coupling the FNTD with borated cell samples.

Deciphering Binding Potential of Naphthalimide-Coumarin Conjugate with c-MYC G-Quadruplex for Developing Anticancer Agents: A Spectroscopic and Molecular Modeling Approach.

It has been well accumulated that G-quadruplex (G4-DNA) has great anticancer relevance, and various heterocyclic moieties have been synthesized and examined as potent G4-DNA binders with promising anticancer activity. Here, we have synthesized a series of naphthalimide-triazole-coumarin conjugates by substituting various amines and further examine their anticancer activity against 60 human cancer cell lines at 10 μM. One and five dose concentration results reveal low values of MG-MID GI50 for compounds including 8a (3.18 μM), 8b (13.11 μM), 8e (7.68 μM) and 8f (1.75 μM). Further cell apoptosis manifests that all compounds can induce cell apoptosis in cancer cells by stabilizing the c-MYC promoter G-quadruplex. Therefore, the G-quadruplex-mediated pathway may be responsible for the apoptosis that these naphthalimide-coumarin compounds caused in cancer cells. Therefore, multispectroscopic techniques are employed to evaluate the binding of molecules with c-MYC G4-DNA where all four molecules readily bind to G4-DNA and stabilize it with a high binding constant, leading to inhibition of cancer cells and apoptosis of cancer cells. Binding studies toward ct-DNA disclose that these compounds do not interact with ds-DNA and thus selectively target G4-DNA to exert their anticancer activity. All the active compounds have greater affinity toward Human Serum Albumin (HSA) and can readily bind with HSA with a binding constant of 12 × 104 M-1 (8a), 13.0 × 104 M-1 (8b), 14.2 × 104 M-1 (8e), 16.3 × 104 M-1 (8f). Thus, the results disclose that inhibition and killing of cancer cells by these derivatives feasibly occur due to their ability to interact with c-MYC G-quadruplex forming promoters and their high affinity toward HSA unfold potent anticancer agents and can be taken further for clinical trials.

Abstract IA10: Immune side effects in ferroptosis-targeted therapy

Abstract Ferroptosis, a regulated form of cell death driven by lipid peroxidation, has emerged as a promising strategy in cancer therapy, complementing established modalities such as chemotherapy, immunotherapy, and radiotherapy. While the mechanisms of ferroptosis are highly context-dependent, the classical approach to inducing ferroptosis involves targeting the GPX4 (glutathione peroxidase 4) pathway. GPX4 is a critical enzyme that detoxifies lipid hydroperoxides (L-OOH) by reducing them to non-toxic lipid alcohols (L-OH) using glutathione (GSH) as a cofactor, thereby preventing lipid peroxidation and ferroptotic cell death. Although targeting GPX4 effectively induces ferroptosis in cancer cells, its widespread expression in both tumor and normal cells presents challenges. Direct inhibition of GPX4 can lead to unintended immune cell death, potentially impairing antitumor immunity by reducing the activity of cytotoxic T cells and other immune effectors essential for robust immune responses. This immunosuppressive effect could undermine the therapeutic benefits of ferroptosis-targeted therapies. To overcome this limitation, alternative strategies have been explored. For instance, non-direct targeting of GPX4, such as inducing TRIM25-mediated degradation of GPX4, has shown promise in selectively killing cancer cells while sparing normal tissues and preserving immune function. This approach minimizes toxicity and maintains the activity of key immune cells, including cytotoxic T cells, enhancing the overall efficacy of ferroptosis-based treatments. Understanding the potential risks and immune-related side effects of ferroptosis-targeted therapies is critical for their successful clinical translation. Citation Format: Daolin Tang. Immune side effects in ferroptosis-targeted therapy. [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 IA10

NanoTrackThera Platform for Real-Time, In Situ Monitoring of Tumor Immunotherapy and Photothermal Synergistic Efficacy.

Cancer is one of the leading causes of death worldwide, posing a significant threat to human health. Although immunotherapy has shown promise in cancer treatment, its efficacy is often compromised by tumor immune evasion, which hinders treatment outcomes. Therefore, combining immunotherapy with other therapeutic approaches to enhance its effectiveness has become an increasingly accepted strategy in clinical practice. In response to this need, a nanotechnology-based platform, NanoTrackThera (NTT), which enables both combination therapy and real-time efficacy diagnosis, is developed. Using nonsmall cell lung cancer (NSCLC) as a model, the NTT platform integrates immunotherapy and photothermal therapy (PTT) to enhance the activity of natural killer (NK) cells, employ immune checkpoint inhibitors, and leverage the heat generation from self-assembled nanoparticles under near-infrared (NIR) irradiation to directly kill cancer cells. Simultaneously, the nanoplatform incorporates dual detection capabilities through fluorescence imaging and photoacoustic imaging. With these multimodal imaging techniques, the platform can achieve real-time, in situ, tracking of tumor biomarker changes during treatment, providing precise feedback on the efficacy of the combined immunotherapy and photothermal therapy. The NTT platform significantly enhances therapeutic efficacy while enabling real-time monitoring of dynamic changes in key tumor biomarkers, providing a solution for personalized and adaptive precision therapy.

Natural killer cell engagers for cancer immunotherapy.

This review article explores the rapidly evolving field of bi-, tri-, and multi-specific NK cell engagers (NKCEs), highlighting their potential as a cutting-edge approach in cancer immunotherapy. NKCEs offer a significant advancement over conventional monoclonal antibodies (mAbs) by enhancing Antibody-Dependent Cellular Cytotoxicity (ADCC). They achieve this by stably and selectively binding to both NK cell activating receptors and tumor-associated antigens (TAAs). Unlike traditional mAbs, which depend on the relatively transient interaction between their Fc region and CD16a, NKCEs establish more robust connections with a range of activating receptors (e.g., CD16a, NKG2D, NKp30, NKp46, NKG2C) and inhibitory receptors (e.g., Siglec-7) on NK cells, thereby increasing cancer cell killing efficacy and specificity. This review article critically examines the strategies for engineering bi-, tri-, and multi-specific NKCEs for cancer immunotherapy, providing an in-depth analysis of the latest advancements in NKCE platform technologies currently under development by pharmaceutical and biotech companies and discussing the preclinical and clinical progress of these products. While NKCEs show great promise, the review underscores the need for continued research to optimize their therapeutic efficacy and to overcome obstacles related to NK cell functionality in cancer patients. Ultimately, this article presents an overview of the current landscape and future prospects of NKCE-based cancer immunotherapy, emphasizing its potential to revolutionize cancer treatment.

Polycarbonate-Based Polymersome Photosensitizers with Cell-Penetrating Properties for Improved Killing of Cancer Cells.

Polymer-based photosensitizers have found various applications in photodynamic therapy (PDT). However, the absence of targeting ability commonly results in a substantial reduction in photosensitizer accumulation at the tumor site, significantly limiting the therapeutic efficacy of the system. In addition, the development of biodegradable polymeric photosensitizers is of critical importance for biological applications. In this work, we present the development of guanidine-functionalized biodegradable photosensitizers based on poly(trimethylene carbonate) (PTMC) block copolymers, which can self-assemble into polymersomes. The presence of guanidine groups on the surface of polymersomes can significantly enhance the cellular uptake efficiency of photosensitizers, thereby improving the intracellular production of reactive oxygen species (ROS). The in vitro study demonstrates that the guanidinylated polymersome photosensitizers can promote the killing of cancer cells compared to unfunctionalized polymersomes in the presence of light irradiation. The guanidine-functionalized PTMC-based polymersome photosensitizers, with the integration of cell-targeting ability and biodegradability, are anticipated to provide a novel strategy for developing advanced biomedical polymer systems for PDT.