Unveiling the promising anticancer effect of copper-based compounds: a comprehensive review.

Copper is a necessary micronutrient for maintaining the well-being of the human body. The biological activity of organic ligands, especially their anticancer activity, is often enhanced when they coordinate with copper(I) and (II) ions. Copper and its compounds are capable of inducing tumor cell death through various mechanisms of action, including activation of apoptosis signaling pathways by reactive oxygen species (ROS), inhibition of angiogenesis, induction of cuproptosis, and paraptosis. Some of the copper complexes are currently being evaluated in clinical trials for their ability to map tumor hypoxia in various cancers, including locally advanced rectal cancer and bulky tumors. Several studies have shown that copper nanoparticles can be used as effective agents in chemodynamic therapy, phototherapy, hyperthermia, and immunotherapy. Despite the promising anticancer activity of copper-based compounds, their use in clinical trials is subject to certain limitations. Elevated copper concentrations may promote tumor growth, angiogenesis, and metastasis by affecting cellular processes.

Omega-3 polyunsaturated fatty acid derived lipid mediators: a comprehensive update on their application in anti-cancer drug discovery.

INTRODUCTION: ω-3 Polyunsaturated fatty acids (PUFAs) have a range of health benefits, including anticancer activity, and are converted to lipid mediators that could be adapted into pharmacological strategies. However, the stability of these mediators must be improved, and they may require formulation to achieve optimal tissue concentrations. AREAS COVERED: Herein, the author reviews the literature around chemical stabilization and formulation of ω-3 PUFA mediators and their application in anticancer drug discovery. EXPERT OPINION: Aryl-urea bioisosteres of ω-3 PUFA epoxides that killed cancer cells targeted the mitochondrion by a novel dual mechanism: as protonophoric uncouplers and as inhibitors of electron transport complex III that activated ER-stress and disrupted mitochondrial integrity. In contrast, aryl-ureas that contain electron-donating substituents prevented cancer cell migration. Thus, aryl-ureas represent a novel class of agents with tunable anticancer properties. Stabilized analogues of other ω-3 PUFA-derived mediators could also be adapted into anticancer strategies. Indeed, a cocktail of agents that simultaneously promote cell killing, inhibit metastasis and angiogenesis, and that attenuate the pro-inflammatory microenvironment is a novel future anticancer strategy. Such regimen may enhance anticancer drug efficacy, minimize the development of anticancer drug resistance and enhance outcomes.

PEGylated chitosan-coated nanophotosensitizers for effective cancer treatment by photothermal-photodynamic therapy combined with glutathione depletion.

The combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has emerged as a promising strategy for cancer treatment. However, the poor photostability and photothermal conversion efficiency (PCE) of organic small-molecule photosensitizers, and the intracellular glutathione (GSH)-mediated singlet oxygen scavenging largely decline the antitumor efficacy of PTT and PDT. Herein, a versatile nanophotosensitizer (NPS) system is developed by ingenious incorporation of indocyanine green (ICG) into the PEGylated chitosan (PEG-CS)-coated polydopamine (PDA) nanoparticles via multiple π-π stacking, hydrophobic and electrostatic interactions. The PEG-CS-covered NPS showed prominent colloidal and photothermal stability as well as high PCE (ca 62.8 %). Meanwhile, the Michael addition between NPS and GSH can consume GSH, thus reducing the GSH-induced singlet oxygen scavenging. After being internalized by CT26 cells, the NPS under near-infrared laser irradiation produced massive singlet oxygen with the aid of thermo-enhanced intracellular GSH depletion to elicit mitochondrial damage and lipid peroxide formation, thus leading to ferroptosis and apoptosis. Importantly, the combined PTT and PDT delivered by NPS effectively inhibited CT26 tumor growth in vivo by light-activated intense hyperthermia and redox homeostasis disturbance. Overall, this work presents a new tactic of boosting antitumor potency of ICG-mediated phototherapy by PEG-CS-covered NPS.

Local Production of Acute Phase Proteins: A Defense Reaction of Cancer Cells to Injury with Focus on Fibrinogen.

This review is intended to demonstrate that the local production of acute phase proteins (termed local acute phase response (lAPR)) and especially fibrin/fibrinogen (FN) is a defense mechanism of cancer cells to therapy, and inhibition of the lAPR can augment the effectiveness of cancer therapy. Previously we detected a lAPR accompanying tumor cell death during the treatment of triple-negative breast cancer (TNBC) with modulated electro-hyperthermia (mEHT) in mice. We observed a similar lAPR in in hypoxic mouse kidneys. In both models, production of FN chains was predominant among the locally produced acute phase proteins. The production and extracellular release of FN into the tumor microenvironment is a known method of self-defense in tumor cells. We propose that the lAPR is a new, novel cellular defense mechanism like the heat shock response (HSR). In this review, we demonstrate a potential synergism between FN inhibition and mEHT in cancer treatment, suggesting that the effectiveness of mEHT and chemotherapy can be enhanced by inhibiting the HSR and/or the lAPR. Non-anticoagulant inhibition of FN offers potential new therapeutic options for cancer treatment.

Using birth-death processes to infer tumor subpopulation structure from live-cell imaging drug screening data.

Tumor heterogeneity is a complex and widely recognized trait that poses significant challenges in developing effective cancer therapies. In particular, many tumors harbor a variety of subpopulations with distinct therapeutic response characteristics. Characterizing this heterogeneity by determining the subpopulation structure within a tumor enables more precise and successful treatment strategies. In our prior work, we developed PhenoPop, a computational framework for unravelling the drug-response subpopulation structure within a tumor from bulk high-throughput drug screening data. However, the deterministic nature of the underlying models driving PhenoPop restricts the model fit and the information it can extract from the data. As an advancement, we propose a stochastic model based on the linear birth-death process to address this limitation. Our model can formulate a dynamic variance along the horizon of the experiment so that the model uses more information from the data to provide a more robust estimation. In addition, the newly proposed model can be readily adapted to situations where the experimental data exhibits a positive time correlation. We test our model on simulated data (in silico) and experimental data (in vitro), which supports our argument about its advantages.

Inorganic nanoparticles for photothermal treatment of cancer.

In recent years, inorganic nanoparticles (NPs) have attracted increasing attention as potential theranostic agents in the field of oncology. Photothermal therapy (PTT) is a minimally invasive technique that uses nanoparticles to produce heat from light to kill cancer cells. PTT requires two essential elements: a photothermal agent (PTA) and near-infrared (NIR) radiation. The role of PTAs is to absorb NIR, which subsequently triggers hyperthermia within cancer cells. By raising the temperature in the tumor microenvironment (TME), PTT causes damage to the cancer cells. Nanoparticles (NPs) are instrumental in PTT given that they facilitate the passive and active targeting of the PTA to the TME, making them crucial for the effectiveness of the treatment. In addition, specific targeting can be achieved through their enhanced permeation and retention effect. Thus, owing to their significant advantages, such as altering the morphology and surface characteristics of nanocarriers comprised of PTA, NPs have been exploited to facilitate tumor regression significantly. This review highlights the properties of PTAs, the mechanism of PTT, and the results obtained from the improved curative efficacy of PTT by utilizing NPs platforms.

Supramolecular self-assembled gold nanoparticle clusters for synergistic photothermal-chemo tumor therapy.

The combination of photothermal therapy and chemotherapy has emerged as a promising strategy to improve cancer therapeutic efficacy. However, developing a versatile nanoplatform that simultaneously possesses commendable photothermal effect and high drug encapsulation efficiency remains a challenging problem yet to be addressed. Herein, we report a facile supramolecular self-assembly strategy to construct gold nanoparticle clusters (AuNCs) for synergistic photothermal-chemo therapy. By utilizing the functional polysaccharide as a targeted ligand, hyaluronic acid-enriched AuNCs were endowed with targeting CD44 receptor overexpressed on the B16 cancer cells. Importantly, these hyaluronic acid modified AuNCs can shelter therapeutic cargo of doxorubicin (DOX) to aggregate larger nanoparticles via a host-guest interaction with the anchored ß-cyclodextrin, as a "nanocluster-bomb" (DOX@AuNCs). The in vitro results revealed that these DOX@AuNCs showed light-triggered drug release behavior and synergistic photothermal-chemo therapy. The improved efficacy of synergistic therapy was further demonstrated by treating a xenografted B16 tumor model in vivo. We envision that our multipronged design of DOX@AuNCs provides a potent theranostic platform for precise cancer therapy and could be further enriched by introducing different imaging probes and therapeutic drugs as appropriate suitable guest molecules.

Engineering a hyaluronic acid-encapsulated tumor-targeted nanoplatform with sensitized chemotherapy and a photothermal effect for enhancing tumor therapy.

Chemotherapy remains one of the most widely used cancer treatment modalities in clinical practice. However, the characteristic microenvironment of solid tumors severely limits the anticancer efficacy of chemotherapy. In addition, a single treatment modality or one death pathway reduces the antitumor outcome. Herein, tumor-targeting O2 self-supplied nanomodules (CuS@DOX/CaO2-HA) are proposed that not only alleviate tumor microenvironmental hypoxia to promote the accumulation of chemotherapeutic drugs in tumors but also exert photothermal effects to boost drug release, penetration and combination therapy. CuS@DOX/CaO2-HA consists of copper sulfide (CuS)-loaded calcium peroxide (CaO2) and doxorubicin (DOX), and its surface is further modified with HA. CuS@DOX/CaO2-HA underwent photothermal treatment to release DOX and CaO2. Hyperthermia accelerates drug penetration to enhance chemotherapeutic efficacy. The exposed CaO2 reacts with water to produce Ca2+, H2O2 and O2, which sensitizes cells to chemotherapy through mitochondrial damage caused by calcium overload and a reduction in drug efflux via the alleviation of hypoxia. Moreover, under near infrared (NIR) irradiation, CuS@DOX/CaO2-HA initiates a pyroptosis-like cell death process in addition to apoptosis. In vivo, CuS@DOX/CaO2-HA demonstrated high-performance antitumor effects. This study provides a new strategy for synergistic enhancement of chemotherapy in hypoxic tumor therapy via combination therapy and multiple death pathways.

Tumor Microenvironment-Triggered Self-Adaptive Polymeric Photosensitizers for Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) employs photosensitizers to convert nearby oxygen into toxic singlet oxygen (1O2) upon laser light irradiation, showing great potential as a noninvasive approach for tumor ablation. However, the therapeutic efficacy of PDT is essentially impeded by π-π stacking and the aggregation of photosensitizers. Herein, we propose a tumor microenvironment-triggered self-adaptive nanoplatform to weaken the aggregation of photosensitizers by selenium-based oxidation at the tumor site. The selenide units in a selenium-based porphyrin-containing amphiphilic copolymer (PSe) could be oxidized into hydrophilic selenoxide units, leading to the nanoplatform self-expansion and stretching of the distance between intramolecular porphyrin units. This process could provide a better switch to greatly reduce the aggregation of photosensitive porphyrin units, generating more 1O2 upon laser irradiation. As verified in a series of in vitro and in vivo studies, PSe could be efficiently self-adapted at tumor sites, thus significantly enhancing the PDT therapeutic effect against solid tumors and minimizing side effects.

Antioxidants activities of phytochemicals perspective modulation of autophagy and apoptosis to treating cancer.

The study of chemicals extracted from natural sources should be encouraged due to the significant number of cancer deaths each year and the financial burden imposed by this disease on society. The causes of almost all cancers involve a combination of lifestyle, environmental factors, and genetic and inherited factors. Modern medicine researchers are increasingly interested in traditional phytochemicals as they hold potential for new bioactive compounds with medical applications. Recent publications have provided evidence of the antitumor properties of phytochemicals, a key component of traditional Chinese medicine, thereby opening new avenues for their use in modern medicine. Various studies have demonstrated a strong correlation between apoptosis and autophagy, two critical mechanisms involved in cancer formation and regulation, indicating diverse forms of crosstalk between them. Phytochemicals have the ability to activate both pro-apoptotic and pro-autophagic pathways. Therefore, understanding how phytochemicals influence the relationship between apoptosis and autophagy is crucial for developing a new cancer treatment strategy that targets these molecular mechanisms. This review aims to explore natural phytochemicals that have demonstrated anticancer effects, focusing on their role in regulating the crosstalk between apoptosis and autophagy, which contributes to uncontrolled tumor cell growth. Additionally, the review highlights the limitations and challenges of current research methodologies while suggesting potential avenues for future research in this field.

Ursolic acid alleviates cancer cachexia by inhibiting STAT3 signaling pathways in C2C12 myotube and CT26 tumor-bearing mouse model.

Cancer cachexia, a multi-organ disorder resulting from tumor and immune system interactions, prominently features muscle wasting and affects the survival of patients with cancer. Ursolic acid (UA) is known for its antioxidant, anti-inflammatory, and anticancer properties. However, its impact on cancer cachexia remains unexplored. This study aimed to assess the efficacy of UA in addressing muscle atrophy and organ dysfunction in cancer cachexia and reveal the mechanisms involved. UA dose-dependently ameliorated C2C12 myotube atrophy. Mechanistically, it inhibited the expression of muscle-specific RING finger containing protein 1 (MURF1) and the phosphorylation of signal transducer and activator of transcription 3 (STAT3), and upregulated the mRNA or protein levels of myogenic differentiation antigen and myogenin in cultured C2C12 myotubes treated with conditioned medium. In vivo, UA protected CT26 tumor-bearing mice against loss of body weight, as well as increased skeletal muscle and epididymal fat without affecting tumor growth. Additionally, UA increased food intake in CT26 tumor-bearing mice. The mRNA expression of tumor necrosis-α and interleukin 6 was significantly downregulated in the intestine, gastrocnemius, and heart tissues following 38 d UA administration. UA treatment reversed the levels of myocardial function indicators, including creatine kinase, creatine kinase-MB, lactate dehydrogenase, car-dial troponin T, and glutathione. Finally, UA treatment significantly inhibited the expression of MURF1, the phosphorylation of nuclear factor kappa-B p65, and STAT3 in the gastrocnemius muscle and heart tissues of cachexic mice. Our findings suggest that UA is a promising natural compound for developing dietary supplements for cancer cachexia therapy owing to its anti-catabolic effects.

Cancer cell plasticity: from cellular, molecular, and genetic mechanisms to tumor heterogeneity and drug resistance.

Cancer is a complex disease displaying a variety of cell states and phenotypes. This diversity, known as cancer cell plasticity, confers cancer cells the ability to change in response to their environment, leading to increased tumor diversity and drug resistance. This review explores the intricate landscape of cancer cell plasticity, offering a deep dive into the cellular, molecular, and genetic mechanisms that underlie this phenomenon. Cancer cell plasticity is intertwined with processes such as epithelial-mesenchymal transition and the acquisition of stem cell-like features. These processes are pivotal in the development and progression of tumors, contributing to the multifaceted nature of cancer and the challenges associated with its treatment. Despite significant advancements in targeted therapies, cancer cell adaptability and subsequent therapy-induced resistance remain persistent obstacles in achieving consistent, successful cancer treatment outcomes. Our review delves into the array of mechanisms cancer cells exploit to maintain plasticity, including epigenetic modifications, alterations in signaling pathways, and environmental interactions. We discuss strategies to counteract cancer cell plasticity, such as targeting specific cellular pathways and employing combination therapies. These strategies promise to enhance the efficacy of cancer treatments and mitigate therapy resistance. In conclusion, this review offers a holistic, detailed exploration of cancer cell plasticity, aiming to bolster the understanding and approach toward tackling the challenges posed by tumor heterogeneity and drug resistance. As articulated in this review, the delineation of cellular, molecular, and genetic mechanisms underlying tumor heterogeneity and drug resistance seeks to contribute substantially to the progress in cancer therapeutics and the advancement of precision medicine, ultimately enhancing the prospects for effective cancer treatment and patient outcomes.

Tocotrienol isoforms: The molecular mechanisms underlying their effects in cancer therapy and their implementation in clinical trials.

Tocotrienols are found in a variety of natural sources, like rice bran, annatto seeds and palm oil, and have been shown to have several health-promoting properties, particularly against chronic diseases such as cancer. The incidence of cancer is rapidly increasing around the world, not only a result of continued aging and population growth, but also due to the adoption of aspects of the Western lifestyle, such as high-fat diets and low-physical activity. The literature provides strong evidence that tocotrienols are able to inhibit the growth of various cancers, including breast, lung, ovarian, prostate, liver, brain, colon, myeloma and pancreatic cancers. These findings, along with the reported safety profile of tocotrienols in healthy human volunteers, encourage further research into these compounds' potential use in cancer prevention and treatment. The current review provided detailed information about the molecular mechanisms of action of different tocotrienol isoforms in various cancer models and evaluated the potential therapeutic effects of different vitamin E analogues on important cancer hallmarks, such as cellular proliferation, apoptosis, angiogenesis and metastasis. MEDLINE/PubMed and Scopus databases were used to identify recently published articles that investigated the anticancer effects of vitamin E derivatives in various types of cancer in vitro and in vivo along with clinical evidence of adjuvant chemopreventive benefits. Following an overview of pre-clinical studies, we describe several completed and ongoing clinical trials that are paving the way for the successful implementation of tocotrienols in cancer chemotherapy.

A computational tumor growth model experience based on molecular dynamics point of view using deep cellular automata.

Cancer, as identified by the World Health Organization, stands as the second leading cause of death globally. Its intricate nature makes it challenging to study solely based on biological knowledge, often leading to expensive research endeavors. While tremendous strides have been made in understanding cancer, gaps remain, especially in predicting tumor behavior across various stages. The integration of artificial intelligence in oncology research has accelerated our insights into tumor behavior, right from its genesis to metastasis. Nevertheless, there's a pressing need for a holistic understanding of the interactions between cancer cells, their microenvironment, and their subsequent interplay with the broader body environment. In this landscape, deep learning emerges as a potent tool with its multifaceted applications in diverse scientific challenges. Motivated by this, our study presents a novel approach to modeling cancer tumor growth from a molecular dynamics' perspective, harnessing the capabilities of deep-learning cellular automata. This not only facilitates a microscopic examination of tumor behavior and growth but also delves deeper into its overarching behavioral patterns. Our work primarily focused on evaluating the developed tumor growth model through the proposed network, followed by a rigorous compatibility check with traditional mathematical tumor growth models using R and Matlab software. The outcomes notably aligned with the Gompertz growth model, accentuating the robustness of our approach. Our validated model stands out by offering adaptability to diverse tumor growth datasets, positioning itself as a valuable tool for predictions and further research.

Assembling Ag2S quantum dots onto peptide nanosheet as a biomimetic two-dimensional nanoplatform for synergistic near infrared-II fluorescent imaging and photothermal therapy of tumor.

Fluorescent bioimaging and photothermal therapy (PTT) techniques have potential significance in cancer diagnosis and treatment and have been widely applied in biomedical and practical clinical trials. This study proposes the molecular design and biofabrication of a two-dimensional (2D) nanoplatform, exhibiting promising prospects for synergistic bioimaging and PTT of tumors. First, biocompatible 2D peptide nanosheets (PNSs) were designed and prepared through peptide self-assembly. These served as a support matrix for assembling polyethylene glycol-modified Ag2S quantum dots (PEG-Ag2SQDs) to form a 2D nanoplatform (PNS/PEG-Ag2SQDs) with unique fluorescent and photothermal properties. The designed 2D nanoplatform not only showed improved photothermal efficacy and an elevated photothermal conversion efficiency of 52.46 %, but also demonstrated significant lethality against tumors in both in vitro and in vivo cases. Additionally, it displays excellent imaging effects in the near-infrared II region, making it suitable for synergistic fluorescent imaging-guided PTT of tumors. This study not only provides a facile approach for devising and synthesizing 2D peptide assemblies but also presents new biomimetic strategies to create functional 2D organic/inorganic nanoplatforms for biomedical applications.

Intracellular Magnetic Hyperthermia Enables Concurrent Down-Regulation of CD47 and SIRPα To Potentiate Antitumor Immunity.

Harnessing the potential of tumor-associated macrophages (TAMs) to engulf tumor cells offers promising avenues for cancer therapy. Targeting phagocytosis checkpoints, particularly the CD47-signal regulatory protein α (SIRPα) axis, is crucial for modulating TAM activity. However, single checkpoint inhibition has shown a limited efficacy. In this study, we demonstrate that ferrimagnetic vortex-domain iron oxide (FVIO) nanoring-mediated magnetic hyperthermia effectively suppresses the expression of CD47 protein on Hepa1-6 tumor cells and SIRPα receptor on macrophages, which disrupts CD47-SIRPα interaction. FVIO-mediated magnetic hyperthermia also induces immunogenic cell death and polarizes TAMs toward M1 phenotype. These changes collectively bolster the phagocytic ability of macrophages to eliminate tumor cells. Furthermore, FVIO-mediated magnetic hyperthermia concurrently escalates cytotoxic T lymphocyte levels and diminishes regulatory T cell levels. Our findings reveal that magnetic hyperthermia offers a novel approach for dual down-regulation of CD47 and SIRPα, reshaping the tumor microenvironment to stimulate immune responses, culminating in significant antitumor activity.

Bimetallic Gold/Silver and Bioactive Camptothecin Hybrid Nanoparticles for Eradication of Cancer Stem Cells in a Combination Manner.

The defeat of cancer is still a challenge due to the existence of cancer stem cells (CSCs) because they resist conventional chemotherapy via multifactor regulated mechanisms. Consequently, one-dimensional action toward CSCs cannot work. Herein, we used rationally designed hybrid nanoparticles as a combined cancer therapy, hoping to form a multidimensional control network. In this paper, gold/silver alloy nanoparticle decorated camptothecin nanocrystals were formulated according to complementary anti-CSC mechanisms from gold, silver, and organic drug. This smart drug formulation could combine chemotherapy and thermotherapy, target different tumor sites, and demonstrate versatile toxicity profiles from each component. Major results indicated that this nanosystem demonstrated indiscriminately effective cytotoxic/proapoptotic/necrotic activity against bulk MCF-7 cells and their CSC subpopulation, in particular under laser ablation. Moreover, this nanosystem displayed enhanced antineoplastic activity against CSC spheroids, resulting in a significant reduction in their number and size, that is, their self-renewal capacity. All the results indicated that CSCs upon treatment of these new hybrid nanoparticles underwent reduced stemness and conversion from the original quiescent state and recovered their sensitivity toward chemotherapy. The relevant anticancer mechanism was ascribed to NIR-pH dual responsive drug release, synergistic/combined thermo-chemotherapy of organic drug and inorganic alloy nanoparticles, enhanced cellular uptake mediated by alloy nanoparticles, and Ag+-induced biomembrane damage. This thermo-chemotherapy platform provides a new combinatorial strategy for inorganic and organic agents in the complete elimination of CSCs.

Self-Delivery Nanomedicines Reverse Thermal Resistance to Enhance Tumor Mild-Temperature Photothermal Therapy.

Tumoral thermal defense mechanisms considerably attenuate the therapeutic outcomes of mild-temperature photothermal therapy (PTT). Thus, developing a simple, efficient, and universal therapeutic strategy to sensitize mild-temperature PTT is desirable. Herein, we report self-delivery nanomedicines ACy NPs comprising a near-infrared (NIR) photothermal agent (Cypate), mitochondrial oxidative phosphorylation inhibitor (ATO), and distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000), which have a high drug-loading efficiency that can reverse tumoral thermal resistance, thereby increasing mild-temperature PTT efficacy. ACy NPs achieved targeted tumor accumulation and performed NIR fluorescence imaging capability in vivo to guide tumor PTT for optimized therapeutic outcomes. The released ATO reduced intracellular ATP levels to downregulate multiple heat shock proteins (including HSP70 and HSP90) before PTT, which reversed the thermal resistance of tumor cells, contributing to the excellent results of mild-temperature PTT in vitro and in vivo. Therefore, this study provides a simple, biosafe, advanced, and universal heat shock protein-blocking strategy for tumor PTT.

The Graphene Quantum Dots Gated Nanoplatform for Photothermal-Enhanced Synergetic Tumor Therapy.

Currently, the obvious side effects of anti-tumor drugs, premature drug release, and low tumor penetration of nanoparticles have largely reduced the therapeutic effects of chemotherapy. A drug delivery vehicle (MCN-SS-GQDs) was designed innovatively. For this, the mesoporous carbon nanoparticles (MCN) with the capabilities of superior photothermal conversion efficiency and high loading efficiency were used as the skeleton structure, and graphene quantum dots (GQDs) were gated on the mesopores via disulfide bonds. The doxorubicin (DOX) was used to evaluate the pH-, GSH-, and NIR-responsive release performances of DOX/MCN-SS-GQDs. The disulfide bonds of MCN-SS-GQDs can be ruptured under high glutathione concentration in the tumor microenvironment, inducing the responsive release of DOX and the detachment of GQDs. The local temperature of a tumor increases significantly through the photothermal conversion of double carbon materials (MCN and GQDs) under near-infrared light irradiation. Local hyperthermia can promote tumor cell apoptosis, accelerate the release of drugs, and increase the sensitivity of tumor cells to chemotherapy, thus increasing treatment effect. At the same time, the detached GQDs can take advantage of their extremely small size (5-10 nm) to penetrate deeply into tumor tissues, solving the problem of low permeability of traditional nanoparticles. By utilizing the photothermal properties of GQDs, synergistic photothermal conversion between GQDs and MCN was realized for the purpose of synergistic photothermal treatment of superficial and deep tumor tissues.

Cancer-Thylakoid Hybrid Membrane Camouflaged Thulium Oxide Nanoparticles with Oxygen Self-Supply Capability for Tumor-Homing Phototherapy.

Nanomaterials that generate reactive oxygen species (ROS) upon light irradiation have significant applications in various fields, including photodynamic therapy (PDT) that is widely recognized as a highly momentous strategy for the eradication of cancer cells. However, the ROS production rate of photosensitizers, as well as the tumor hypoxia environment, are two major challenges that restrict the widespread application of PDT. In this study, a cancer-thylakoid hybrid membrane-camouflaged thulium oxide nanoparticles (Tm2O3) for tumor-homing phototherapy through dual-stage-light-guided ROS generation and oxygen self-supply is developed. Tm2O3 as a type II photosensitizer are viable for NIR-stimulated ROS generation due to the unique energy levels, large absorption cross section, and long lifetime of the 3H4 state of Tm ions. The thylakoid membrane (TK) plays a catalase-like role in converting hydrogen peroxide into oxygen and also acts as a natural photosensitizer that can generate lethal ROS through electron transfer when exposed to light. In addition, fluorescence dye DiR is embedded in the hybrid membrane for in vivo tracing as well as photothermal therapy. Results show that tumors in Tm2O3@TK-M/DiR group are effectively ablated following dual-stage-light irradiation, highlighting the promising potential of rare-earth element-based type II photosensitizers in various applications.