Strategy For Cancer Treatment Research Articles

The Mechanisms of Immune Evasion in Cancer Stem Cells and Related Immunotherapy Advances

Cancer Stem Cells (CSCs), as a unique subset of tumor cells, play a crucial role in tumor initiation, progression, and recurrence due to their self-renewal and differentiation capabilities. CSCs exhibit significant immune evasion abilities, allowing them to escape host immune surveillance, leading to the failure of conventional treatments. This paper reviews the definition, characteristics, and immune evasion mechanisms of CSCs, including immune checkpoint pathways, immunosuppressive microenvironment, and changes in surface antigen expression. Additionally, it explores various immunotherapies targeting CSCs, such as immune checkpoint inhibitors, CAR-T cell therapy, tumor vaccines, and other emerging therapies, discussing their research progress and clinical application prospects. By comprehensively understanding the immune evasion mechanisms of CSCs and related immunotherapies, we aim to provide new insights and strategies for future cancer treatments.

Optimizing breast cancer diagnosis: Harnessing the power of nature-inspired metaheuristics for feature selection with soft voting classifiers

Breast cancer is a widespread and serious condition that poses a significant threat to women's health globally, contributing significantly to mortality rates. Machine learning tools play a critical role in both the effective management and early detection of this disease. Feature selection (FS) methods are essential for identifying the most impactful features to improve breast cancer diagnosis. These methods reduce data dimensionality, eliminate irrelevant information, enhance learning accuracy, and improve the comprehensibility of results. However, the increasing complexity and dimensionality of cancer data pose substantial challenges to many existing FS methods, thereby reducing their efficiency and effectiveness. To overcome these challenges, numerous studies have demonstrated the success of nature-inspired optimization (NIO) algorithms across various domains. These algorithms excel in mimicking natural processes and efficiently solving complex optimization problems. Building on these advancements, we propose an innovative approach that combines powerful feature selection methods based on NIO techniques with a soft voting classifier. The NIO techniques employed include the Genetic Algorithm, Cuckoo Search, Salp Swarm, Jaya, Flower Pollination, Whale Optimization, Sine Cosine, Harris Hawks, and Grey Wolf Optimization algorithms. The Soft Voting Classifier integrates various machine learning models, including Support Vector Machines, Gaussian Naive Bayes, Logistic Regression, Decision Tree, and Gradient Boosting. These are used to improve the effectiveness and accuracy of breast cancer diagnosis. The proposed approach has been empirically evaluated using a variety of evaluation measures, such as F1 score, precision, recall, accuracy and Area Under the Curve (AUC), for performance comparison with individual machine learning techniques. The results demonstrate that the soft-voting ensemble technique, particularly when combined with feature selection based on the Jaya algorithm, outperforms all individual classifiers on the breast cancer dataset. It achieves the highest scores for accuracy, precision, recall, F1-score, and AUC, with values of 99.6 %, 99.21 %, 100 %, 99.6 %, and 99.6 %, respectively. Following closely, both the Genetic Algorithm and Salp Swarm feature selection demonstrate strong performance, with scores of 99.5 %, 100 %, 99 %, 99.5 %, and 99.5 %, respectively. Furthermore, the approach's effectiveness in identifying the minimal set of relevant features has been evaluated. Given the critical importance of selecting relevant features in complex cancer datasets, the proposed method proves to be a valuable tool for achieving early detection and improved interpretability. This method can also support healthcare professionals in making well-informed decisions regarding cancer diagnosis and treatment strategies.

Construction and validation of a pancreatic cancer prognostic model based on genes related to the hypoxic tumor microenvironment.

Pancreatic cancer is one of the most lethal malignancies, characterized by poor prognosis and low survival rates. Traditional prognostic factors for pancreatic cancer offer inadequate predictive accuracy, often failing to capture the complexity of the disease. The hypoxic tumor microenvironment has been recognized as a significant factor influencing cancer progression and resistance to treatment. This study aims to develop a prognostic model based on key hypoxia-related molecules to enhance prediction accuracy for patient outcomes and to guide more effective treatment strategies in pancreatic cancer. To develop and validate a prognostic model for predicting outcomes in patients with pancreatic cancer using key hypoxia-related molecules. This pancreatic cancer prognostic model was developed based on the expression levels of the hypoxia-associated genes CAPN2, PLAU, and CCNA2. The results were validated in an independent dataset. This study also examined the correlations between the model risk score and various clinical features, components of the immune microenvironment, chemotherapeutic drug sensitivity, and metabolism-related pathways. Real-time quantitative PCR verification was conducted to confirm the differential expression of the target genes in hypoxic and normal pancreatic cancer cell lines. The prognostic model demonstrated significant predictive value, with the risk score showing a strong correlation with clinical features: It was significantly associated with tumor grade (G) (b P < 0.01), moderately associated with tumor stage (T) (a P < 0.05), and significantly correlated with residual tumor (R) status (b P < 0.01). There was also a significant negative correlation between the risk score and the half-maximal inhibitory concentration of some chemotherapeutic drugs. Furthermore, the risk score was linked to the enrichment of metabolism-related pathways in pancreatic cancer. The prognostic model based on hypoxia-related genes effectively predicts pancreatic cancer outcomes with improved accuracy over traditional factors and can guide treatment selection based on risk assessment.

Machine learning- a new paradigm in nanoparticle-mediated drug delivery to cancerous tissues through the human cardiovascular system enhanced by magnetic field

Nanoparticle-mediated drug delivery offers a promising approach to targeted cancer therapy, leveraging the ability of nanoparticles to deliver therapeutic agents directly to cancerous tissues with minimal impact on surrounding healthy cells. The presence of these nanoparticles is governed by a concentration equation, which accounts for the diffusion, convection, and reaction of the nanoparticles with the blood components. It is well-known that whenever a disease or infection occurs in a human, in 80% of cases a rise in the concentration of hydrogen peroxide in the blood occurs. This is the reason why blood is assumed to contain hydrogen peroxide (in the present study), which is a biomarker of oxidative stress and inflammation. This study explores the integration of machine learning (ML) techniques into the optimization of drug delivery processes within the human cardiovascular system, focusing on the enhancement of these processes through the application of magnetic fields. By employing ML algorithms, we analyze and predict the behavior of nanoparticles as they navigate the complex fluid dynamics of the cardiovascular system, particularly under the influence of an external magnetic field. The predictive power of ML models enables the precise control of nanoparticle trajectories, optimizing their accumulation in cancerous tissues and improving the efficacy of the drug delivery system. The findings of this study demonstrate that ML-enhanced magnetic targeting can significantly enhance the precision and effectiveness of nanoparticle-mediated drug delivery, offering a new paradigm in cancer treatment strategies. This approach has the potential to revolutionize the field by providing personalized and highly efficient therapeutic solutions for cancer patients.

Wireless Light‐Emitting Diode‐Driven Functional Microneedle Devices for Skin Cancer Therapy

AbstractPhotodynamic therapy, a noninvasive cancer treatment strategy, is a promising remedy for malignant skin cancers. However, treatment of skin cancer with this method requires sufficient photosensitizer molecules to permeate into cancer cells before illumination for effective activation to induce potent reactive oxygen species for eliminating cancer cells. However, transdermal drug delivery using conventional photosensitizers faces major challenges due to skin barriers, diminishing the effectiveness of drug penetration and therapeutic efficacies. To overcome these limitations, biocompatible, physiologically dissolvable, and optically activatable functional microneedle devices are applied for effective percutaneous penetration of drug molecules into solid tumors in a murine model. The proposed wireless light‐emitting diode light‐driven functional microneedle device that effectively induces apoptosis of cancer cells and disruption of the tumor area and can enhance in vitro, ex vivo, and in vivo drug‐delivery effectiveness for treating skin cancer. The design and strategy of the present functional microneedle devices can help shed light on future advanced cancer therapy.

Deciphering Internal Regulatory Patterns within the p53 Core Tetramer: Insights from Community Network Analysis.

Gene therapy is one of the most effective strategies for cancer treatment. The p53 protein, commonly known as the "guardian of the genome", plays a critical role in gene activation and tumor suppression. Tetramerization of the p53 core domain is an essential allosteric process that supports its suppression functions. This letter presents a framework to analyze the structure, function, and dynamic connectivity of the p53 tetramer, using community network analysis based on all-atom molecular dynamics simulations. The communities within the p53 monomer exhibit distinct functional roles, while interactions between molecules establish a symmetrical network structure. We identified direct evidence of single, double, and multiple pathway regulations within the p53 tetramer and crucial residue pairs involved in these connections. Our study provides a comprehensive framework to understand the community network of the p53 tetramer, offering new insights into the stable formation of the p53 core tetramer.

Plant-derived glycosides in cancer treatment: diverse strategies for tumor suppression

Plant-derived glycosides have emerged as promising candidates for cancer therapy due to their diverse biological activities. These compounds exert their anti-cancer effects through multiple mechanisms, including apoptosis induction, cell cycle arrest, inhibition of angiogenesis, suppression of metastasis, and immune modulation. Cardiac glycosides, flavonoid glycosides, and saponins are among the key types of glycosides showing potential in preclinical studies. By selectively targeting cancer cells, these glycosides demonstrate the ability to induce programmed cell death and interfere with cancer progression without harming normal cells. In addition, their role in inhibiting blood vessel formation and reducing cancer cell spread positions them as valuable components of future cancer treatment strategies. Preclinical evidence, supported by emerging clinical data, underscores the potential of plant-derived glycosides as novel agents in oncology, either as standalone treatments or in combination with conventional therapies. Ongoing research will determine their full therapeutic potential in cancer management.

Global trends and topics in CDK7 inhibitor research: a bibliometric analysis.

CDK7 has been demonstrated to play a crucial role in the initiation and progression of malignancy. Therefore, targeting CDK7, which regulates the transcription process, has emerged as a new promising approach for treating cancer. Research on CDK7 inhibitors has significantly increased over the past 2decades, with almost 600 related papers in the Web of Science Core Collection database. To effectively identify future research hotspots and potential future directions, it is crucial to systematically review and visually present the research on this topic from a comprehensive viewpoint, ensuring scientific reliability. This study performed bibliometric analysis via CiteSpace and VOSviewer scientometrics analysis software to examine data on the publication of articles on CDK7 inhibitors over the past 2decades; the data included country of publication, author names, institution names, scientific categories, cited journals, and keywords related to the field of CDK7 inhibitors. This bibliometric analysis included 426 publications from 41 different nations, referencing a total of 15,892 sources. Research associated with CDK7 inhibitors has rapidly expanded since 2016, and the US and China are the two countries with the highest publication output among the countries and institutes that produce literature on CDK7 inhibitors. Furthermore, the US is the country that most frequently engages in international cooperation. The evolution of keywords identifying antitumor strategies related to CDK7-mediated cellular transcription processes has been the research focus in recent years. In this study, we identified research efforts and their evolving patterns and predicted advances in the CDK7 inhibitor field. The knowledge structure of CDK7 inhibitors encompasses pharmacological mechanisms, therapeutic targets, and cancer treatment strategies. The primary objectives of contemporary research are to discover the processes underlying cancer progression, identify specific signaling pathways, and develop effective clinical medicines.

Light-Promoted Lysosomal Escape of a Phthalocyanine and Antisense Oligonucleotide-Complexed G-Quadruplex for Dual Photodynamic and Antisense Therapy.

Combination therapy has been proven as an effective strategy for cancer treatment. To this end, we report herein a self-assembled nucleic acid-based complex for dual photodynamic and antisense therapy. It contains a nucleolin-targeting As1411-based G-quadruplex platform, a partially hybridized antisense oligonucleotide 4625, which can inhibit the antiapoptotic protein B cell lymphoma-xL inducing apoptotic cell death, and a zinc(II) phthalocyanine (ZnPc)-based photosensitizer held by noncovalent interactions. Through a series of in vitro experiments, we have demonstrated that this DNA complex can be internalized selectively to nucleolin-overexpressed MCF-7 and A549 cells through receptor-mediated endocytosis and is localized in the lysosomes. Upon light irradiation, the photosensitization of ZnPc triggers the formation of reactive oxygen species for cell killing and promotes the lysosomal escape of 4625 for antisense therapy. The combined therapeutic effect can eliminate the cancer cells effectively with a half maximal inhibitory concentration of ca. 0.5 μM.

Apoptosis, autophagy, ferroptosis, and pyroptosis in cisplatin-induced ototoxicity and protective agents.

Cisplatin is widely used to treat various solid tumors. However, its toxicity to normal tissues limits its clinical application, particularly due to its ototoxic effects, which can result in hearing loss in patients undergoing chemotherapy. While significant progress has been made in preclinical studies to elucidate the cellular and molecular mechanisms underlying cisplatin-induced ototoxicity (CIO), the precise mechanisms remain unclear. Moreover, the optimal protective agent for preventing or mitigating cisplatin-induced ototoxicity has yet to be identified. This review summarizes the current understanding of the roles of apoptosis, autophagy, ferroptosis, pyroptosis, and protective agents in cisplatin-induced ototoxicity. A deeper understanding of these cell death mechanisms in the inner ear, along with the protective agents, could facilitate the translation of these agents into clinical therapeutics, help identify new therapeutic targets, and provide novel strategies for cisplatin-based cancer treatment.

MCPIP1 Elicits a Therapeutic Effect on Cervical Cancer by Facilitating XIAP mRNA Decay via Its Endoribonuclease Activity.

Cervical cancer is the fourth most common malignancy in women globally. Chemotherapies, targeted therapies, and immunotherapies in the treatment of cervical cancer are usually accompanied by effective and adverse effects. Therefore, finding other efficient and accurate molecular targets remains essential to improve the treatment benefits of cervical cancer patients. MCPIP1 (monocyte chemoattractant protein-induced protein 1) is a kind of endonuclease with a CCCH zinc finger domain and a PilT-N-terminal (PIN) domain, and its function in cervical cancer is unknown. We found that MCPIP1 inhibits cell proliferation and promotes cell apoptosis of cervical cancer. Additionally, MCPIP1 suppresses mRNA and protein expression of the apoptotic inhibitor XIAP by decreasing its mRNA stability. Mechanically, MCPIP1 binds to the XIAP mRNA via its CCCH zinc finger domain and degrades the XIAP mRNA via the endonuclease activity coming from its PIN domain. Our study clarifies that MCPIP1 promotes cervical cancer cell apoptosis by suppressing the expression of XIAP, thereby impeding cervical cancer progression. Moreover, targeted delivery of MCPIP1 with engineered Salmonella typhimurium leads to tumor growth retardation in the HeLa xenograft tumor model in mice. Therefore, our study may provide a theoretical basis for formulating clinical treatment strategies for cervical cancer.

Advancing Lung Cancer Treatment with Combined c-Met Promoter-Driven Oncolytic Adenovirus and Rapamycin.

Lung cancer remains a formidable health challenge due to its high mortality and morbidity rates. Non-small cell lung cancer (NSCLC) constitutes approximately 85% of all lung cancer cases, with small cell lung cancer (SCLC) accounting for the remainder. Both NSCLC and SCLC cells express receptor tyrosine kinases, which may be overexpressed or mutated in lung cancer, leading to increased activation. The c-Met receptor tyrosine kinase, crucial for cell transformation and tumor growth, invasion, and metastasis, became the focus of our study. We used an E1B55KD-deleted, replication-selective oncolytic adenovirus (Ad.What), driven by the c-Met promoter, targeting lung cancer cells with c-Met overexpression, thus sparing normal cells. Previous studies have shown the enhanced antitumor efficacy of oncolytic adenoviruses when combined with chemotherapeutic agents. We explored combining rapamycin, a selective mTOR inhibitor with promising clinical trial outcomes for various cancers, with Ad.What. This combination increased infectivity by augmenting the expression of coxsackievirus and adenovirus receptors and αV integrin on cancer cells and induced autophagy. Our findings suggest that combining a c-Met promoter-driven oncolytic adenovirus with rapamycin could be an effective lung cancer treatment strategy, offering a targeted approach to exploit lung cancer cells' vulnerabilities, potentially marking a significant advancement in managing this deadly disease.

Enzymatic interlocking aptamer-micelles for enhanced cellular internalization and nucleus-targeted cancer phototherapy

Multifunctional micelles that permit both diagnosis and treatment present enormous advantage and potential for precision medicine. However, the inherent complexities and structural instability of these systems often cause unsatisfactory targeting and therapeutic performances. Herein, by ingenious design of a 2,5-bis(2-thienyl)pyrrole (SNS) modifier to covalently link with AS1411 aptamer and lipid segment, a simple strategy is proposed for one-step enzymatic preparation of interlocked aptamer-micelle (IApM) under bio-friendly conditions. The interlocked poly(SNS) skeleton in IApM can not only stabilize the micelle structure but also enhance near-infrared (NIR) absorption ability, thus further enhancing cellular internalization and photothermal therapy. In addition, the multivalent AS1411 aptamers tethered in the hydrophilic shell can simultaneously increase the specific binding affinity of DNA micelles and induce nucleus-targeted accumulation for DNA damage-triggered apoptosis. This DNA micelle achieves “best of both worlds” with enhanced biostability for cellular internalization and improved NIR photothermal conversion efficiency for nucleus-targeted therapy, which provides a promising formulation strategy for precision cancer treatment.

Extrachromosomal DNA Associates with Nuclear Condensates and Reorganizes Chromatin Structures to Enhance Oncogenic Transcription.

Extrachromosomal, circular DNA (ecDNA) is a prevalent oncogenic alteration in cancer genomes, often associated with aggressive tumor behavior and poor patient outcome. While previous studies proposed a chromatin-based mobile enhancer model for ecDNA-driven oncogenesis, its precise mechanism and impact remains unclear across diverse cancer types. Our study, utilizing advanced multi-omics profiling, epigenetic editing, and imaging approaches in three cancer models, reveals that ecDNA hubs are an integrated part of nuclear condensates and exhibit cancer-type specific chromatin connectivity. Epigenetic silencing of the ecDNA-specific regulatory modules or chemically disrupting liquid-liquid phase separation breaks down ecDNA hubs, displaces MED1 co-activator binding, inhibits oncogenic transcription, and promotes cell death. These findings substantiate the trans -activator function of ecDNA and underscore a structural mechanism driving oncogenesis. This refined understanding expands our views of oncogene regulation and opens potential avenues for novel therapeutic strategies in cancer treatment.

Comparative Efficacy of 21 Treatment Strategies for Resectable Pancreatic Cancer: A Network Meta-Analysis.

The primary treatment for operable pancreatic cancer (PC) involves surgery followed by adjuvant therapy. Nevertheless, perioperative or neoadjuvant chemotherapy (CT) may be used to mitigate the likelihood of recurrence and mortality. This network meta-analysis (NMA) assesses the comparative efficacy of various treatment approaches for resectable PC. A thorough search was carried out on January 31, 2023, encompassing PubMed/MEDLINE, Cochrane Library, and Embase databases. We incorporated randomized clinical trials (RCTs) that compared surgical interventions with or without (neo)adjuvant or perioperative therapies for operable PC. We conducted a fixed-effects Bayesian NMA. We presented the effect sizes in terms of hazard ratios (HRs) for overall survival (OS) along with 95% credible intervals (95% CrIs). The treatment was deemed statistically superior when the 95% credible interval (CrI) did not encompass a null value (hazard ratio < 1). Treatment rankings were established based on the surface under the cumulative ranking curve (SUCRA). A total of 24 studies were incorporated, comparing 21 treatments with surgery in isolation. Eleven treatments showed superior efficacy compared to surgery alone, with HRs ranging from 0.38 for perioperative treatments to 0.73 for adjuvant 5-fluorouracil. After the exclusion of studies conducted in Asia, it was found that the perioperative regimen of gemcitabine combined with nab-paclitaxel was the most effective regimen (SUCRA, p = 0.99). The findings endorse the utilization of perioperative CT, especially multi-agent CT, as the favored intervention for operable PC in Western nations.

Review on different Multimodal Approaches for Multifactorial Cancer Disease

In early-stage cancer, chemotherapy, radiotherapy or surgery is a common treatment. However, monotherapy results in medicine struggle besides later numerous series of treatment; it loses its effect in patients. The multimodal approach is an elementary principle for treating maximum tumor categories by confirmed existence benefits. The multidisciplinary approach comprises multimodality action and surgery followed by radiotherapy with or lacking chemotherapy or simultaneous chemoradiotherapy is mandatory for diverse forms of tumor. In all pathological states including cancer, combination approach is considered as future of therapeutics. Thus, grouping of multidrug treatment is utmost frequently utilized strategy in cancer treatment. While combining cancer treatment together with anticancer drugs overcomes the medicine fighting as well as provides synergistic result displaying delayed existence for patients. The drive of present review article is to 1) climax necessity and importance of multidisciplinary method in cancer treatment; 2) discuss part of radiotherapy, chemotherapy, immunotherapy and their combinations.

Senolytic effect of triterpenoid complex from Ganoderma lucidum on adriamycin-induced senescent human hepatocellular carcinoma cells model in vitro and in vivo.

Ganoderma lucidum (G. lucidum) is a famous medicinal mushroom that has been reported to prevent and treat a variety of diseases. Different extractions from G. lucidum have been used to manage age-related diseases, including cancer. Nevertheless, the senolytic activity of G. lucidum against senescent cancer cells has not been investigated. Although cellular senescence causes tumor growth inhibition, senescent cells promote the growth of the neighboring tumor cells through paracrine effects. Therefore, the elimination of senescent cells is a new strategy for cancer treatment. In this study, senescence was triggered in HCC cells by the chemotherapeutic agent Adriamycin (ADR), and subsequently, cells were treated with TC to assess its senolytic activity. We found for the first time that the triterpenoid complex (TC) from G. lucidum had senolytic effect, which could selectively eliminate adriamycin (ADR)-induced senescent cells (SCs) of hepatocellular carcinoma (HCC) cells via caspase-dependent and mitochondrial pathways-mediated apoptosis and reduce the levels of senescence markers, thereby inhibiting the progression of cancers caused by SCs. TC could block autophagy at the late stage in SCs, resulting in a significant activation of TC-induced apoptosis. Furthermore, TC inhibited the senescence-associated secretory phenotype (SASP) in SCs through the inhibition of NF-κB, TFEB, P38, ERK, and mTOR signaling pathways and reducing the number of SCs. Sequential administration of ADR and TC in vivo significantly reduced tumor growth and reversed the toxicity of ADR. A triterpenoid complex isolated from G. lucidum may serve as a novel senolytic agent against SCs, and its combination with chemotherapeutic agents may enhance their antitumor efficacy.

Modern strategy of metastatic colorectal cancer treatment (literature review)

Modern strategy of metastatic colorectal cancer treatment (literature review)

Novel Treatment Strategies for Low-Risk Metastatic Castration-Sensitive Prostate Cancer.

The treatment strategy for metastatic castration-sensitive prostate cancer (mCSPC) has changed significantly in recent years. Based on various guidelines, an upfront androgen receptor signaling inhibitor (ARSI) is the first choice, but in patients of Asian descent, including Japanese patients, there are a certain number of cases in which androgen deprivation therapy (ADT) and CAB are more effective. If patients can be identified who show a marked response to ADT within 12 weeks after the initiation of ADT, which is the inclusion criterion for ARSI clinical trials targeting mCSPC, it would be valuable from an economic standpoint. A total of 218 patients with pure prostate adenocarcinoma and treated with ADT at the Kanazawa University Hospital between January 2000 and December 2020 were included in this study. As a risk classification for mCSPC, in addition to the LATITUDE and CHAARTED criteria, we used the castration-sensitive prostate cancer classification proposed by Kanazawa University (Canazawa), developed by the Department of Urology of Kanazawa University. The Canazawa classification was based on three factors: Gleason pattern 5, bone scan index (BSI) ≥ 1.5, and lactate dehydrogenase (LDH) ≥ 300 IU/L. It defined patients with one factor or less as low-risk and patients with two or three factors as high-risk. The overall survival (OS) and time to castration resistance (TTCR) were estimated retrospectively using the Kaplan-Meier method, and factors associated with TTCR were identified using univariate and multivariate analyses. The median follow-up period was 40.4 months, the median OS period was 85.2 months, and the median TTCR period was 16.4 months. The Canazawa risk classification provided the clearest distinction between the OS and TTCR in mCSPC patients. Multivariate analysis revealed a decrease in PSA levels of <95% at 12 weeks after ADT initiation and was a predictor of short TTCR in low-risk, low-volume patients across all risk classifications. The Canazawa classification differentiated the prognosis of mCSPC patients more clearly. A PSA reduction rate of <95% at 12 w after starting ADT in low-risk, low-volume patients of all risk classifications was significantly shorter than the TTCR. We propose a new treatment strategy, in which patients with low-risk mCSPC are treated with ADT and switched to ARSIs based on the rate of PSA reduction at 12 w.

A nanotheranostics with hypoxia-switchable fluorescence and photothermal effect for hypoxia imaging-guided immunosuppressive tumor microenvironment modulation

Modulating the immunosuppressive tumor immune microenvironment (TIME) is considered a promising strategy for cancer treatment. However, effectively modulating the immunosuppressive TIME within hypoxic zones remains a significant challenge. In this work, we developed a hypoxia-responsive amphiphilic drug carrier using boron-dipyrromethene (BODIPY) dye-modified chitosan (CsB), and then fabricated a hypoxia-targeted nanotheranostic system, named CsBPNs, through self-assembly of CsB and pexidartinib (5-((5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl)-N-((6-(trifluoromethyl)pyridin-3-yl)methyl), PLX3397), an immunotherapeutic drug targeting tumor-associated macrophages (TAMs), for synergistic photothermal/immunotherapy and hypoxia imaging. CsBPNs demonstrated uniform size, good stability, and hypoxia-switchable fluorescence and photothermal effects, enabling deep penetration and hypoxia imaging capacities in three-dimensional tumor cell spheres and tumor tissues. In vitro and in vivo experiments showed that CsBPNs under laser irradiation promoted TAMs repolarization, reversed the immunosuppressive TIME, and enhanced the therapeutic outcome of PLX3397 in solid tumors by facilitating deep delivery into hypoxic regions and synergistic photothermal therapy. This work provides a new strategy for detecting and modulating the immunosuppressive TIME in hypoxic zones, potentially enabling more precise and effective photo-immunotherapy in the future.