Multimodal Therapy Research Articles

Phase 1 trial of intraperitoneal paclitaxel in patients with gastric adenocarcinoma and carcinomatosis or positive cytology.

The purpose of this phase 1 trial was to evaluate the safety and toxicity of repeated normothermic intraperitoneal paclitaxel (PTX) for patients with gastric cancer metastatic to the peritoneum. A Bayesian optimal interval design was used to prospectively identify the safety and tolerability of escalating doses of intraperitoneal paclitaxel at weekly treatments for 3 weeks, followed by a 1-week break, and then three additional treatments. The primary objective was to define the maximum tolerated dose. Secondary end points included safety, tolerability, and antitumor activity. A total of 25 patients were treated between January 2020 and April 2023. Five dose-limiting toxicities were observed at 100 mg/m2. Treatment-related grade 3-4 toxicity included leukopenia (32%) and neutropenia (32%). Seven patients required a schedule change to every other week treatments. The maximum tolerated dose for intraperitoneal PTX was 100 mg/m2. The peritoneum post-intraperitoneal PTX demonstrated progression in five (20%), stable disease in five (20%), improvement in 10 (40%), and not evaluable in five (20%). Eight patients (32%) had resolution of their peritoneal disease and seven (28%) underwent attempted resection. The median overall survival (OS) from the diagnosis of metastatic disease was 18.8 months and from the date of treatment initiation was 10.8 months. One-, 2-, and 3-year OS rates from the diagnosis of metastatic disease were 84%, 38%, and 25%, respectively. Paclitaxel may be safely used at intraperitoneal doses of 100 mg/m2. Neutropenia associated with weekly treatments was common. Peritoneal complete clinical response rates with multimodality therapy including PTX were promising.

Treatment resistant cushing's disease following standard and novel multi-modal therapy in the setting of a constitutional pathogenic MSH2 variant

Treatment resistant cushing's disease following standard and novel multi-modal therapy in the setting of a constitutional pathogenic MSH2 variant

Fabrication of a novel macrophage-targeted biomimetic delivery composite hydrogel with multiple-sensitive properties for tri-modal combination therapy of rheumatoid arthritis

In this study, a porous polydopamine (PDA) nanoparticle-decorated β-glucan microcapsules (GMs) nanoplatform (PDA/GMs) were developed with macrophage-targeted biomimetic features and a carriers-within-carriers structure. Indocyanine green (ICG) and catalase (CAT) were subsequently co-encapsulated within the PDA/GMs to create a multifunctional nanotherapeutic agent, termed CIPGs. Furthermore, CIPGs and sinomenine (SIN) were co-loaded within a thermo-sensitive hydrogel to design an injectable delivery system, termed CIPG/SH, with potential for multi-modal therapy of rheumatoid arthritis (RA). Photothermal studies indicated that the CIPGs hold excellent photothermal conversion ability and thermal stability, as they combined the photothermal performance of both PDA and ICG. Meanwhile, the CIPGs displayed favorable oxygen self-supplying and photodynamic performance. The CIPGs showed near-infrared (NIR)-induced phototoxicity, effectively inhibiting macrophage proliferation and displaying remarkable antibacterial activity. In vitro drug release from the prepared CIPG/SH showed a controlled release pattern. Animal experiments conducted on an RA mice model confirmed that the formulated CIPG/SH exhibited significant therapeutic effects. By integrating the biological advantages, photothermal/photodynamic performance of the CIPGs, and controlled drug release performance of the thermo-sensitive hydrogels in a single delivery system, the prepared injectable CIPG/SH represents a novel versatile delivery system with great potential for multi-modal combination targeting therapy in RA.

Non-pharmacological interventions to treat mood disturbances post-stroke: a systematic review

ABSTRACT Background Stroke survivors face high rates of depression, anxiety, and pseudobulbar affect. Clinicians report lack of clarity on effective non-pharmacological interventions due to uncertainty about treatment options as barriers to evidence-based treatment. No systematic review has investigated the effectiveness of non-pharmacological interventions on the conditions of depression, anxiety, and pseudo-bulbar affect. Objectives The aim of this study was to evaluate the effectiveness of non-pharmacological interventions on the outcomes of depression, anxiety, and pseudobulbar affect in post-stroke individuals. Methods Following the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched databases Medline, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and PsycINFO for randomized controlled trials in English, within 2012–2023, evaluating the effect of a non-pharmacological intervention on depression, anxiety, and/or pseudobulbar affect. Two researchers screened titles, abstracts, and full texts. One researcher extracted data and assessed risk of bias. Data were synthesized narratively. Results Forty-two studies were included. Intervention types included education (n = 9), psychological therapy (n = 8), and physical exercise (n = 8). Intervention types reporting positive outcomes for depression were psychological therapy (n = 6), physical exercise (n = 3) and robot-assisted therapy (n = 3). Intervention types effective in improving anxiety were physical exercise (n = 2), psychological therapy (n = 3) and multi-modal therapy approaches (n = 2). No studies explored the impact on pseudobulbar affect. Conclusion Non-pharmacological interventions may be effective in improving mood in stroke survivors. Robot-assisted therapy and physical exercise were seen to improve multiple outcome measures. Patient education should be delivered alongside rehabilitation and directed to both stroke-survivor and caregiver.

30 Microbiota and Companion Animal Health

Abstract The intestinal microbiota has been shown to have an important role in health and disease of animals. It is a complex system that depends on interactions between the luminal environment and specific bacterial taxa and their function (e.g., production of short-chain fatty acids, conversion of bile acids). Dietary substrates are an important factor for microbial metabolism and supplements have the potential to help in maintaining intestinal health. Major changes in the microbiota and their loss of function (dysbiosis) are mainly associated with antibiotic treatment and in chronic intestinal disease likely due to chronic remodeling of the epithelium. Therefore, often these changes persist long-term. Chronic enteropathies (CE) occur very commonly in dogs and cats, and are frustrating to treat due to lack of specific markers. The pathophysiology is complex and includes changes in the immune system (e.g., inflammation), intestinal function, and the intestinal microbiome. The current classification based on treatment response (i.e., food- vs. steroid-responsive) is currently being questioned, as new research findings indicate that CE is a syndrome with many overlapping unspecific features, often with chronic irreversible changes in intestinal function and dysbiosis. The presentation will summarize novel research about the pathophysiology and novel concepts in multi-modal therapy to these conditions. This program will help better understand the role of the intestinal microbiota in health and disease (with focus on acute diarrhea and chronic intestinal inflammation). New diagnostic methods for evaluation of the intestinal microbiota will be covered. Finally, this lecture will review how to best manage the clinical signs of acute and chronic diarrhea. This includes new evidence of the negative impact of antibiotics on the microbiome and the critical role nutrition can play in managing these patients.

The role of procedural factors on the outcomes of embolization followed by radiosurgery for the treatment of brain arteriovenous malformations: systematic review and proportional meta-analyses.

Multimodal therapy for brain arteriovenous malformations (bAVM) with embolization followed by stereotactic radiosurgery (E + SRS) has shown varying outcomes. Its benefits over other treatment modalities have been questioned. The goal of this systematic review was to determine the factors associated with cure and complication rates of this treatment strategy. A literature search in Medline and Global Index Medicus, from inception to October 2023, was performed. Studies reporting relevant outcome data from bAVM patients treated with E + SRS were included. Data on several patient, lesion and procedure-related factors were collected. Embolization intent was classified as Targeted (of high-risk features), Devascularizing (feeder embolization/flow reduction) and Occluding (intent-to-cure, nidus embolization). The primary outcome was obliteration rate. Secondary outcomes were post-SRS bleeding (PSB), post-embolization neurological complications (PENC) and post-SRS neurological complications (PSNC). Subgroup analyses included embolic agent, embolization intent and radiosurgery type. Proportional meta-analyses and meta-regressions were performed. Forty-one studies were included in the review. The pooled obliteration rate was 56.45% (95% CI 50.94 to 61.88). Meta-regression analyses showed higher obliteration rates with Copolymers and lower obliteration rates with Devascularizing embolization. The pooled PSB, PENC and PSNC rates were 5.50%, 13.75% and 5.02%, respectively. Meta-regression analyses showed higher rates of PSB, PENC and PSNC with Devascularizing embolization, Liquid & Solid embolic agents and Targeted & Devascularizing intent, respectively. Embolic agent and embolization intent were procedural factors associated with treatment outcomes of E + SRS in the management of bAVM patients. The efficacy and safety profiles favor copolymers as embolic agents and disfavor Devascularizing as embolization intent. The protocol of the systematic review was registered in PROSPERO as CRD42023474171.

Rational Design of a Hetero-multinuclear Gadolinium(III)-Copper(II) Complex: Integrating Magnetic Resonance Imaging, Photoacoustic Imaging, Mild Photothermal Therapy, Chemotherapy and Immunotherapy of Cancer.

For more accurate diagnosis and effective treatment of cancer, we proposed to develop a hetero-multinuclear metal complex based on the property of apoferritin (AFt) for targeting tumor theranostics by integrating dual-modality imaging diagnosis and multimodality therapy. To this end, we rational designed and synthesized a trinuclear Gd(III)-Cu(II) thiosemicarbazone complex (Gd-2Cu) and then constructed a Gd-2Cu@AFt nanoparticle (NP) delivery system. Gd-2Cu/Gd-2Cu@AFt NPs not only had significant T1-weighted magnetic resonance imaging and photoacoustic imaging of the tumor but also effectively inhibited tumor growth through a combination of mild photothermal therapy, chemotherapy, and immunotherapy. Gd-2Cu@AFt NPs optimized the behavior of imaging diagnosis and therapy of Gd-2Cu, improved its targeting ability, and reduced the side effects in vivo. Besides, we revealed and clarified the anticancer mechanism of Gd-2Cu: interrupting energy metabolism of the tumor cell, inducing apoptosis of the tumor cell, and activating a systemic immune response by inducing immunogenic cell death of cancer cells.

Unmasking Disparities in Gallbladder Cancer Outcomes in the Disaggregated Asian American Population

BackgroundGallbladder cancer (GBC) is associated with a high mortality rate. Asian American (AsA) are among the fastest-growing populations in the United States, yet little is known about the disparity of GBC within this cohort. This study identified trends in treatment and outcomes for GBC in a disaggregated fashion, specifically for this population.MethodsA retrospective analysis of the National Cancer Database (NCDB) between 2010 and 2019 examining all patients treated for gallbladder cancer was performed. Basic demographic factors were identified for patients of Caucasian, African American, and disaggregated Asian subpopulations. Survival curves were used to identify differences in median overall survival, and a multivariate analysis was performed to determine which factors impact overall survival.ResultsA total of 1317 (5%) patients were of AsA origin. Median survival for the overall AsA population is 15.1 months compared with Caucasian (11.5 months) and African Americans (11.4 months) (p < 0.0001). Within the AsA groups, the Korean subpopulation had the lowest survival at 12.6 months, whereas Filipinos had the longest survival at 19.1 months (p < 0.0001). Patients of Filipino descent had the highest rate of surgical resection but lower chemotherapy utilization. Conversely, Korean patients had the highest utilization of multimodality therapy. Multivariate analysis demonstrated that belonging to Chinese, Filipino, or Indian ethnicity was associated with decreased risk of mortality.ConclusionsThere are disparate differences in survival for patients with GBC between AsA groups. Socioeconomic, genetic, and epigenetic factors may influence these differences. Further research is needed to delineate the causes of this disparity.

Photoinduction of Ferroptosis and cGAS-STING Activation by a H2S-Responsive Iridium(III) Complex for Cancer-Specific Therapy.

Triggering ferroptosis represents a promising anticancer therapeutic strategy, but the development of a selective ferroptosis inducer for cancer-specific therapy remains a great challenge. Herein, a H2S-responsive iridium(III) complex NA-Ir has been well-designed as a ferroptosis inducer. NA-Ir could selectively light up H2S-rich cancer cells, primarily localize in mitochondria, intercalate into mitochondrial DNA (mtDNA), and induce mtDNA damage, exhibiting higher anticancer activity under light irradiation. Mechanistic studies showed that NA-Ir-mediated PDT triggered lipid peroxidation and glutathione peroxidase 4 downregulation through ROS production and GSH depletion, resulting in ferroptosis through multiple pathways. Moreover, the intense mtDNA damage can activate the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway, leading to ferritinophagy and further ferroptosis. RNA-sequencing analysis showed that NA-Ir-mediated PDT mainly affects the expression of genes related to ferroptosis, autophagy, and cancer immunity. This study demonstrates the first cancer-specific example with ferroptosis and cGAS-STING activation, which provides a new strategy for multimodal synergistic therapy.

MOY 2 - ‘Cachexia Index’ for Prognostication in Surgical Patients with Locally Advanced Oesophageal or Gastric Cancer: A Multicentre Cohort Study

Abstract Background Features of cancer cachexia are known to adversely influence patient outcomes, yet few currently inform clinical decision-making. This study assessed the value of ‘cachexia index’ (CXI), a novel prognostic marker, in patients planned for curative multimodal therapy (neoadjuvant chemotherapy (NAC) and surgery) for oesophagogastric cancer. Methods Consecutive patients newly diagnosed with locally advanced (T3/4 or ≥N1) oesophagogastric cancer were identified through the West of Scotland and South-East Scotland Cancer Networks. CXI was calculated as (L3 skeletal muscle index) x (serum albumin) / (neutrophil-lymphocyte-ratio). Sex-stratified cut-off values were determined based on area under the curve (AUC), and patients were divided into low and normal CXI groups. Primary outcomes of interest were disease progression during NAC and overall survival (≥5-years follow-up). Results Overall, 385 patients (72% male, median 66 years) were treated with NAC for oesophageal (n=274) or gastric (n=111) cancer across the study period. While patients with a low CXI (males: &amp;lt;52 [AUC: 0.691] and females: &amp;lt;41 [AUC: 0.759]) were older and more comorbid, disease characteristics were comparable to those with a normal CXI. Rates of disease progression during neoadjuvant chemotherapy, leading to inoperability, were higher in patients with low CXI (28% vs. 12%, aOR: 3.07 (95% CI: 1.67-5.64), p&amp;lt;0.001). Moreover, low CXI was associated with worsened post-operative mortality (p=0.019) and decreased overall survival (median: 14.9 vs. 56.9 months, aHR: 1.85 (95% CI: 1.42-2.42), p&amp;lt;0.001). Conclusion CXI represents a valuable marker of ‘host stage’, and a potential adjunct to routine tumour staging. This could improve prognostication and decision-making in patients with locally advanced oesophagogastric cancer.

Self-reported Costs of Endometriosis Patients in Germany

AbstractEndometriosis patients face a significant economic burden. In addition to the directly attributable costs of the diagnosis and therapy of endometriosis, such as drug treatment and multimodal pain therapy, various indirect follow-up costs can be expected, e.g., due to incapacity for work and reduced work performance. As already reported in previous publications, endometriosis is associated with considerable costs for the health care system and society as well as for the affected women and their families.In order to measure the extent of the costs associated with endometriosis patients, 250 patients with an average age of 32.80 years were recruited via social media and interviewed about their self-financed costs as part of an online survey. The assessed direct costs comprise inpatient treatments, outpatient or pain therapy, fertility treatments, hormone therapies, prescribed and privately paid medications and aids, other therapeutic procedures, and directly attributable travel costs for endometriosis treatments.This resulted in an average cost of € 2059.55 per year. Indirect costs were calculated based on loss of income, day-to-day support, care costs, costs due to follow-up illnesses and other costs. On average, the indirect costs were € 2174.25. The average costs resulting from the survey totalled € 4233.81 per year with a standard deviation of € 8240.31.An increase of out-of-pocket costs can be assumed. This may result from an improved range of services for alternative treatment methods and an increased awareness of the need for personal investment in health. However, further health economic studies are needed to validate the results.

Olfactory neuroblastoma in children: clinical analysis of five cases

The clinical data of five patients diagnosed with olfactory neuroblastoma (ONB) who were admitted to the Department of Pediatrics, Beijing Tongren Hospital Affiliated to Capital Medical University from January 2012 to January 2024 were retrospectively analyzed. Two males and three females aged 6.2 (5.7-15.8) years were included. The symptoms mainly covered nasal congestion, increased nasal secretions, headache, decreased vision and so on. Pathological grade Ⅱ, Ⅲ and Ⅳ was identified in two cases, one case and two cases, respectively. Modified Kadish stage B, C and D was detected in one case, two cases and two cases, respectively. All patients underwent surgery, chemotherapy, and radiation therapy. Among the five patients, four survived and one died. The follow-up time was 22.3 (10.4-56.4) months, and the recurrence rate was 0. ONB should be suspected when tumors are presented in the upper and middle parts of the nasal cavity, especially dumbbell shaped masses that grow towards the nasal cavity and intracranial area based on imaging. The multimodality therapy of ONB comprising of surgery and chemotherapy, can achieve good therapeutic effects and prognosis, but long-term follow-up is required.

In situ enzymatic peptide-based nanomedicine with combined effects for enhanced tumor radio-immunotherapy

Despite the combination of radiotherapy and immunotherapy in clinical practice have shown promising synergistic anti-tumor effect, the immunosuppressive tumor microenvironment (TME) remains to be one of stumbling block impeding the therapeutic efficacy of radio-immunotherapy. In this study, in situ self-assembled peptide-based drug delivery systems with multiple effects were constructed for enhancing tumor radio-immunotherapy. The two peptide-drug conjugates could co-assembled into peptide-based nanomedicine on the cancer cell membrane under enzyme catalysis and continuously release small molecular active drugs in the cytoplasm, which combined action lead YAP phosphorylation and nuclear transfer failure. By simutaneously suppressing glycolysis and reactivating the dysfunctional Hippo pathway, the peptide-based nanomedicine also remitted the immunosuppressive TME by reducing lactate levels and the expression of immunosuppressive factors, respectively. As a result, the pro-tumorigenic M2 phenotype of tumor-associated macrophages (TAMs) was decreased and the anti-tumorigenic M1 phenotype of TAMs was increased. Such a dual intervention strategy from cellular metabolic level and gene transcription level not only inhibited tumor cell proliferation but also reversed the immunosuppressive TME, thereby augmenting the combined efficacy of radiotherapy and immune checkpoint blockade (ICB) therapy. The work is anticipated to contribute novel insights into anti-cancer drug targeted delivery and tumor multi-modal synergistic therapy.

797. A COMPARATIVE ANALYSIS ON THE EFFECTIVENESS OF DIFFERENT TREATMENT MODALITIES FOR ESOPHAGEAL CARCINOMA; A SYSTEMATIC REVIEW

Abstract Background Esophageal carcinoma; sixth most common cancer worldwide, presents a significant clinical challenge due to its aggressive nature and often late-stage diagnosis, resulting in poor prognosis and limited treatment options. Various treatment modalities, including surgery, chemotherapy, radiation therapy, immunotherapy, and targeted therapy, are utilized in clinical practice. However, the optimal treatment strategy remains uncertain, as the comparative effectiveness of these modalities is not well-defined. Past studies have provided conflicting evidence, necessitating a comprehensive evaluation to guide clinical decision-making. Therefore, this systematic review aims to compare the efficacy and safety of different treatment modalities for esophageal carcinoma, with the objective of informing evidence-based treatment approaches and improving patient outcomes. Methods Total 350 publications from PubMed, EMBASE, Cochrane, Google Scholar and Semantic Scholar databases were identified on the effectiveness of different treatment modalities for esophageal carcinoma between 2000 and 2024. Following deduplication, two independent reviewers initially screened the articles for eligibility with titles and abstracts, and then, with complete articles. Bias assessment using GRADE guidelines for observational studies was done. Non-English studies, case-series/case-reports/essays/book-chapters/conference-abstracts/editorials/thesis/dissertations and studies without full-texts were excluded. Results Overall, the effectiveness of each treatment modality for esophageal carcinoma depends on various factors, including tumor stage, histology, patient characteristics, and treatment regimen. Combination approaches, such as chemoradiotherapy or multimodal therapy, are often used to maximize treatment efficacy and improve patient outcomes. Conclusion Multidisciplinary collaboration, personalized treatment approach, integration of novel therapies, such as immunotherapy and targeted therapy, into standard treatment regimens, survivorship care and advocate for further research to identify optimal treatment sequencing, identify predictive biomarkers of treatment response, and explore novel therapeutic targets to improve outcomes for patients with esophageal carcinoma is recommended.

1755P Multimodal therapy in first line treatment of very high risk Ewing sarcoma patients: Results of the French prospective multicenter COMBINAIR3 phase II trial

1755P Multimodal therapy in first line treatment of very high risk Ewing sarcoma patients: Results of the French prospective multicenter COMBINAIR3 phase II trial

Chronic thromboembolic pulmonary disease.

Chronic thromboembolic pulmonary hypertension is a complication of pulmonary embolism and a treatable cause of pulmonary hypertension. The pathology is a unique combination of mechanical obstruction due to failure of clot resolution, and a variable degree of microvascular disease, that both contribute to pulmonary vascular resistance. Accordingly, multiple treatments have been developed to target the disease components. However, accurate diagnosis is often delayed. Evaluation includes high-quality imaging modalities, necessary for disease confirmation and for appropriate treatment planning. All patients with chronic thromboembolic pulmonary disease, and especially those with pulmonary hypertension, should be referred to expert centres for multidisciplinary team decision on treatment. The first decision remains assessment of operability, and the best improvement in symptoms and survival is achieved by the mechanical therapies, pulmonary endarterectomy and balloon pulmonary angioplasty. With the advances in multimodal therapies, excellent outcomes can be achieved with 3-year survival of >90%.

Regulating Aggregation-Induced Emission Luminogen for Multimodal Imaging-Navigated Synergistic Therapy Involving Anti-Angiogenesis.

As a new avenue for cancer research, phototheranostics has shown inexhaustible and vigorous vitality as it permits real-time diagnosis and concurrent in situ therapy upon non-invasive light-initiation. However, construction of an advanced material, allowing prominent phototheranostic outputs and synchronously surmounting the inherent deficiency of phototheranostics, would be an appealing yet significantly challenging task. Herein, an aggregation-induced emission (AIE)-active luminogen (namely DBD-TM) featured by intensive electron donor-acceptor strength and twisted architecture with finely modulated intramolecular motion, is tactfully designed and prepared. DBD-TM simultaneously possessed fluorescence emission in the second near-infrared (NIR-II) region and high-efficiency photothermal conversion. By integrating DBD-TM with anti-angiogenic agent sorafenib, a versatile nanomaterial is smoothly fabricated and utilized for trimodal imaging-navigated synergistic therapy involving photothermal therapy and anti-angiogenesis toward cancer. This advanced approach is capable of affording accurate tumor diagnosis, complete tumor elimination, and largely restrained tumor recurrence, evidently denoting a prominent theranostic formula beyond phototheranostics. This study will offer a blueprint for exploiting a new generation of cancer theranostics.

Prevention and management of radiotherapy-related toxicities in gynecological malignancies. Position paper on behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology)

Multi-modal therapies for gynecological cancers management may determine a wide range of side effects which depend on therapy-related factors and patient characteristics and comorbidities. Curative or adjuvant pelvic radiotherapy is linked with acute and late toxicity due to irradiation of organs at risk, as small and large bowel, rectum, bladder, pelvic bone, vagina and bone marrow. Successful toxicity management varies with its severity, Radiation Centre practice and experience and skills of radiation oncologists. This position paper was designed by the Italian Association of Radiation and Clinical Oncology Gynecology Study Group to provide radiation oncologists with evidence-based strategies to prevent and manage acute and late toxicities and follow-up recommendations for gynecological cancer patients submitted radiotherapy. Six workgroups of radiation oncologists with over 5 years of experience in gynecologic cancers were setup to investigate radiotherapy-related toxicities. For each topic, PubMed database was searched for relevant English language papers from January 2005 to December 2022. Titles and abstracts of results were checked to verify suitability for the document. Reference lists of selected studies and review papers were added if pertinent. Data on incidence, etiopathogenesis, prevention, treatment and follow-up of acute and late side effects for each organ at risk are presented and discussed.

Multi-Sensitive Au NCs/5-FU@Carr-LA Composite Hydrogels for Targeted Multimodal Anti-Tumor Therapy.

Multifunctional targeted drug delivery systems have been explored as a novel cancer treatment strategy to overcome limitations of traditional chemotherapy. The combination of photodynamic therapy and chemotherapy has been shown to enhance efficacy, but the phototoxicity of traditional photosensitizers is a challenge. In this study, we prepared a multi-sensitive composite hydrogel containing gold nanoclusters (Au NCs) and the temperature-sensitive antitumor drug 5-fluorourac il (5-FU) using carboxymethyl cellulose (Carr) as a dual-functional template. Au NCs were synthesized using sodium borohydride as a reducing agent and potassium as a promoter. The resulting Au NCs were embedded in the Carr hydrogel, which was then conjugated with lactobionic acid (LA) as a targeting ligand. The resulting Au NCs/5-FU@Carr-LA composite hydrogel was used for synergistic photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy. Au NCs/5-FU@Carr-LA releases the drug faster at pH 5.0 due to the acid sensitivity of the Carr polymer chain. In addition, at 50 °C, the release rate of Au NCs/5-FU@Carr-LA is 78.2%, indicating that the higher temperature generated by the photothermal effect is conducive to the degradation of Carr polymer chains. The Carr hydrogel stabilized the Au NCs and acted as a matrix for drug loading, and the LA ligand facilitated targeted delivery to tumor cells. The composite hydrogel exhibited excellent biocompatibility and synergistic antitumor efficacy, as demonstrated by in vitro and in vivo experiments. In addition, the hydrogel had thermal imaging capabilities, making it a promising multifunctional platform for targeted cancer therapy.

Fe-doped biodegradable dendritic mesoporous silica nanoparticles for starvation therapy and photothermal-enhanced cascade catalysis in tumor therapy

Combination therapies have attracted significant attention because they address the limitations of monotherapy while improving overall efficacy. In this study, we designed a novel nanoplatform, named GOx@Fe-DMSN@PDA (GFDP), by integrating Fe2+ into dendritic mesoporous silica nanoparticles (DMSN) and selecting glucose oxidase (GOx) as the model drug loaded into the DMSN pores. Additionally, we coated the surface of the DMSN with polydopamine (PDA) to confer pH/near infrared (NIR) light-responsive controlled-release behavior and photothermal therapy (PTT). The introduction of Fe2+ into the DMSN framework greatly improved biodegradability and enhanced the peroxidase (POD)-like activity of GFDP. In addition, GOx could consume glucose and generate hydrogen peroxide (H2O2) within tumor cells to facilitate starvation therapy and enhance cascade catalysis. The PDA coating provided the DMSN with an intelligent response release ability, promoting efficient photothermal conversion and achieving the PTT effect. Cellular tests showed that under NIR light irradiation, GFDP exhibited a synergistic effect of PTT-enhanced starvation therapy and cascade catalysis, with a half-maximal inhibitory concentration (IC50) of 2.89 μg/mL, which was significantly lower than that of GFDP without NIR light irradiation (18.29 μg/mL). The in vivo anti-tumor effect indicated that GFDP could effectively accumulate at the tumor site for thermal imaging and showed remarkable synergistic therapeutic effects. In summary, GFDP is a promising nanoplatform for multi-modal combination therapy that integrates starvation therapy, PTT, and cascade catalysis.