Effective Tumor Treatment Research Articles

Harnessing the Power of NK Cell Receptor Engineering as a New Prospect in Cancer Immunotherapy.

Natural killer (NK) cells have recently gained popularity as an alternative for cancer immunotherapy. Adoptive cell transfer employing NK cells offers a safer therapeutic option compared to T-cell-based therapies, due to their significantly lower toxicity and the availability of diverse autologous and allogeneic NK cell sources. However, several challenges are associated with NK cell therapies, including limited in vivo persistence, the immunosuppressive and hostile tumor microenvironment (TME), and the lack of effective treatments for solid tumors. To address these limitations, the modification of NK cells to stably produce cytokines has been proposed as a strategy to enhance their persistence and proliferation. Additionally, the overexpression of activating receptors and the blockade of inhibitory receptors can restore the NK cell functions hindered by the TME. To further improve tumor infiltration and the elimination of solid tumors, innovative approaches focusing on the enhancement of NK cell chemotaxis through the overexpression of chemotactic receptors have been introduced. This review highlights the latest advancements in preclinical and clinical studies investigating the engineering of activating, inhibitory, and chemotactic NK cell receptors; discusses recent progress in cytokine manipulation; and explores the potential of combining the chimeric antigen receptor (CAR) technology with NK cell receptors engineering.

Phenanthrene Appending Ruthenium Complexes: DNA Binding, Molecular Docking, TDDFT Calculation, and Photocytoxicity In Vitro

ABSTRACTPhotodynamic therapy (PDT) has been an effective tumor treatment to reduce the side effects of chemotherapy. Herein, we described the synthesis of two Ru (II) complexes by introducing a phenanthrene unit and their photocytotoxicity. Ru1 and Ru2 displayed high DNA affinities by intercalation. Under light, two complexes produced high singlet oxygen (1O2) quantum yields and cleaved DNA efficiently. Both high DNA affinities and 1O2 quantum yields of two complexes resulted in obvious photocytotoxicity towards Hela, A549, and A375 cells. Furthermore, low dark cytotoxicity was also observed for two complexes, which may promote them to act as potential PDT agents. TDDFT (Time‐dependent density functional theory) calculations also demonstrated two complexes that might display the PDT activities via 1O2 photogeneration.

The Role of Redox Environment in Tumors.

Reactive Oxygen Species (ROS) and the redoxin system regulate the redox environment. Thus, they mediate various physiological and pathological processes involved in tumor occurrence and development by activating redox-sensitive genes and regulating redox signaling pathways, including tumor cell proliferation, migration, invasion, and various cell death types. Therefore, the mechanism underlying redox environment regulation must be clarified to accurately target this mechanism and improve the effect of tumor treatment. This review introduces redox-sensitive transcription factors and their activated downstream signaling pathways, and the application of inhibitors targeting related transcription factors in tumor therapy.

Bactofection, Bacterial-Mediated Vaccination, and Cancer Therapy: Current Applications and Future Perspectives.

From the first report in 1891 by Dr. Coley of the effective treatment of tumors in 1000 patients with Streptococcus and the first successful use of bacterial vectors for transferring therapeutic genes in 1980 by Dr. Schnaffer, bactofection has been shown to be a promising strategy in the fields of vaccination, gene therapy, and cancer therapy. This review describes the general theory of bactofection and its advantages, disadvantages, challenges, and expectations, compiling the most notable advances in 14 vaccination studies, 27 cancer therapy studies, and 13 clinical trials. It also describes the current scope of bactofection and promising results. The extensive knowledge of Salmonella biology, as well as the multiple adequacies of the Ty21a vaccination platform, has allowed notable developments worldwide that have mainly been reflected in therapeutic efforts against cancer. In this regard, we strongly recommend the creation of a recombinant Ty21a model that constitutively expresses the GtgE protease from S. typhimurium, allowing this vector to be used in animal trials, thus enhancing the likelihood of favorable results that could quickly transition to clinical trials. From the current perspective, it is necessary to explore a greater diversity of bacterial vectors and find the best combination of implemented attenuations, generating personalized models that guarantee the maximum effectiveness in cancer therapy and vaccination.

Epigenetic reprogramming in gastrointestinal cancer: biology and translational perspectives.

Gastrointestinal tumors, the second leading cause of human mortality, are characterized by their association with inflammation. Currently, progress in the early diagnosis and effective treatment of gastrointestinal tumors is limited. Recent whole-genome analyses have underscored their profound heterogeneity and extensive genetic and epigenetic reprogramming. Epigenetic reprogramming pertains to dynamic and hereditable alterations in epigenetic patterns, devoid of concurrent modifications in the underlying DNA sequence. Common epigenetic modifications encompass DNA methylation, histone modifications, noncoding RNA, RNA modifications, and chromatin remodeling. These modifications possess the potential to invoke or suppress a multitude of genes associated with cancer, thereby governing the establishment of chromatin configurations characterized by diverse levels of accessibility. This intricate interplay assumes a pivotal and indispensable role in governing the commencement and advancement of gastrointestinal cancer. This article focuses on the impact of epigenetic reprogramming in the initiation and progression of gastric cancer, esophageal cancer, and colorectal cancer, as well as other uncommon gastrointestinal tumors. We elucidate the epigenetic landscape of gastrointestinal tumors, encompassing DNA methylation, histone modifications, chromatin remodeling, and their interrelationships. Besides, this review summarizes the potential diagnostic, therapeutic, and prognostic targets in epigenetic reprogramming, with the aim of assisting clinical treatment strategies.

In-situ activated arsenic-molybdenum dual-prodrug nanocomplexes for glutathione-depletion enhanced photothermal/chemotherapy against triple-negative breast cancer

Arsenic trioxide, a traditional chemotherapeutic agent, has limitations in clinical application due to its nonspecific delivery and severe systemic toxicity. To address this challenge, we have capitalized on the promising potential of molybdenum-based materials for tumor diagnosis and treatment. We developed a novel multifunctional arsenic-molybdenum dual-prodrug nanocomposite delivery system (AsMo-NCM) by integrating arsenic compounds with molybdenum compounds. This system leverages elevated glutathione (GSH) levels within tumors for specific activation. Within the tumor microenvironment, the system converts Mo(VI) to the more active Mo(V), enabling combined photothermal therapy and photoacoustic imaging for comprehensive diagnosis and treatment. Furthermore, low-toxicity arsenic(V) is converted into highly toxic trivalent arsenic within the high-GSH tumor microenvironment, thereby enhancing tumor cell apoptosis, reducing toxicity to normal tissues, and synergistically improving treatment outcomes. In addition, AsMo-NCM can be biodegraded and rapidly excreted, reducing concerns about their long-term presence and possible toxic effects. The combination of these approaches maximizes GSH depletion, thereby enhancing the synergistic photothermal/chemotherapy effect of AsMo-NCM for precise and effective tumor treatment, thus offering promising prospects for cancer therapy.

The Impact of MRI-Based Advanced Neuroimaging on Neurooncologists' Clinical Decision-Making in Patients With Posttreatment High-Grade Glioma: A Prospective Survey-Based Study.

Background: Advanced MRI-based neuroimaging techniques, such as perfusion and spectroscopy, have been increasingly incorporated into routine follow-up protocols in patients treated for high-grade glioma (HGG), to help differentiate tumor progression from treatment effect. However, these techniques' influence on clinical management remains poorly understood. Objective: To evaluate the impact of MRI-based advanced neuroimaging on clinical decision-making in patients with HGG in the posttreatment setting. Methods: This prospective study, performed at a comprehensive cancer center from March 1, 2017, to October 31, 2020, included adult patients treated by chemoradiation for WHO grade 4 diffuse glioma who underwent MRIbased advanced neuroimaging (comprising multiple perfusion imaging sequences and spectroscopy) to further evaluate findings on conventional MRI equivocal for tumor progression versus treatment effect. The ordering neuro-oncologists completed surveys before and after each advanced neuroimaging session. The percent of care episodes with a change between the intended and actual management plan on the surveys conducted before and after advanced neuroimaging, respectively, was computed and compared with a previously published percent using the Wald test for independent samples proportions. Results: The study included 63 patients (mean age, 55±13 years; 36 women, 27 men) who underwent 70 advanced neuroimaging sessions. Ordering neuro-oncologists' intended and actual management plans on the surveys completed before and after advanced neuroimaging, respectively, differed in 44% (31/70, [95% CI: 33-56%]) of episodes, which differed from the previously published frequency of 8.5% (5/59) (p<.001). These management plan changes included selection of a different plan for 6/8 episodes with an intended plan to enroll patients in a clinical trial, 12/19 episodes with an intended plan to change chemotherapeutic agents, 4/8 episodes with an intended plan of surgical intervention, and 1/2 episodes with an intended plan of re-irradiation. The ordering neuro-oncologists found advanced neuroimaging to be helpful in 93% (95% CI: 87%-99%) (65/70) of episodes. Conclusion: Neuro-oncologists' management plans changed in a substantial fraction of adult patients with HGG who underwent advanced neuroimaging to further evaluate conventional MRI findings equivocal for tumor progression versus treatment effect. Clinical Impact: The findings support incorporation of advanced neuroimaging into HGG posttreatment monitoring protocols.

Near-infrared circularly polarized light triggered phototherapy based on hybrid CuInSe2 quantum dot hydrogels

For malignant tumor phototherapy, current biomolecules-based materials face challenges such as limited tissue penetration, insufficient tumor accumulation, and overlook of the unique benefits of chirality, thus hampering their phototherapeutic efficiency. Herein, we introduce a novel near-infrared circularly polarized (NIR-CP) light-responsive hybrid CuInSe2@ZnS (CISe@ZnS) quantum dots (QDs) hydrogel (QDs@L/D-Gel), which showcases distinctive NIR chiroptical activity, highly enhanced tumor retention, and superior photothermal/photodynamic properties. Particularly, the QDs@L-Gel exhibits a prominently improved photothermal conversion efficiency (PCE) of 43 % and elevated reactive oxygen species (ROS) upon 808-nm CP light irradiation, outperforming those of linearly polarized light directly emitted from a laser device. Moreover, a remarkably enhanced phototherapeutic efficacy (tumor inhibition rate = 83 %) can be achieved for QDs@L-Gel treated mice after 808-nm CP light treatment, without any toxic side effects. Our findings highlight the importance of supramolecular chirality in NIR-CP-mediated phototherapy, thereby paving a new avenue for more advanced and effective tumor treatment in clinical applications.

Spleen Volume Reduction Is a Reliable and Independent Biomarker for Long-Term Risk of Leukopenia Development in Peptide Receptor Radionuclide Therapy.

177Lu-DOTATATE therapy is an effective treatment for advanced neuroendocrine tumors, despite its dose-limiting hematotoxicity. Herein, the significance of off-target splenic irradiation is unknown. Our study aims to identify predictive markers of peptide receptor radionuclide therapy-induced leukopenia. Methods: We retrospectively analyzed blood counts and imaging data of 88 patients with histologically confirmed, unresectable metastatic neuroendocrine tumors who received 177Lu-DOTATATE treatment at our institution from February 2009 to July 2021. Inclusion criterium was a tumor uptake equivalent to or greater than that in the liver on baseline receptor imaging. We excluded patients with less than 24 mo of follow-up and those patients who received fewer than 4 treatment cycles, additional therapies, or blood transfusions during follow-up. Results: Our study revealed absolute and relative white blood cell counts and relative spleen volume reduction as independent predictors of radiation-induced leukopenia at 24 mo. However, a 30% decline in spleen volume 12 mo after treatment most accurately predicted patients proceeding to leukopenia at 24 mo (receiver operating characteristic area under the curve of 0.91, sensitivity of 0.93, and specificity of 0.90), outperforming all other parameters by far. Conclusion: Automated splenic volume assessments demonstrated superior predictive capabilities for the development of leukopenia in patients undergoing 177Lu-DOTATATE treatment compared with conventional laboratory parameters. The reduction in spleen size proves to be a valuable, routinely available, and quantitative imaging-based biomarker for predicting radiation-induced leukopenia. This suggests potential clinical applications for risk assessment and management.

Targeting Hydrogel for Intelligent Recognition and Spatiotemporal Control in Cell-Based Therapeutics.

Smart drug platforms based on spatiotemporally controlled release and integration of tumor imaging are expected to overcome the inefficiency and uncertainty of traditional theranostic modes. In this study, a composite consisting of a thermosensitive hydrogel (polyvinyl alcohol-carboxylic acid hydrogel (PCF)) and a multifunctional nanoparticle (Fe3O4@Au/Mn(Zn)-4-carboxyphenyl porphyrin/polydopamine (FAMxP))is developed to combine tumor immunogenic cell death (ICD)/immune checkpoint blockade (ICB) therapy under the guidance of magnetic resonance imaging (MRI) and fluorescence imaging (FI). It can not only further recognize the target cells through the folate receptor of tumor cells, but also produce thermal dissolution after exposure to near-infrared light to slowly release FAMxP in situ, thereby prolonging the treatment time and avoiding tumor recurrence. As FAMxP entered the tumor cells, it released FAMx in a pH-dependent manner. Chemodynamic, photothermal and photodynamic therapy can cause significant ICD in cancer cells. ICB can thus be further enhanced by injecting anti-programmed cell death ligand 1, improving the effectiveness of tumor treatment. The developed PCF-FAMxP composite hydrogel may represent an updated drug design approach with simple compositions for cooperative MRI/FI-guided targeted therapeutic pathways for tumors.

Comparison between laparoscopic complete mesocolic excision and D2 radical operation in colon carcinoma resection: A propensity score matching analysis.

Surgery remains the most effective treatment for colon cancer. However, there are still controversies regarding the tumor treatment effect, prognosis, and perioperative impact of complete mesocolic excision (CME) surgery in colon carcinoma resection. This study aims to compare laparoscopic complete mesocolic excision (LCME) and traditional open D2 radical surgery in colon carcinoma resection through a retrospective analysis using 1:1 propensity score matching (PSM). 98 cases undergoing LCME or open D2 colon carcinoma resection at our hospital from January 2014 to November 2021 were retrospectively collected. After excluding cases and 1:1 matching using PSM based on baseline clinical data, 86 patients were assigned in research queue. 43 patients were in each group. Two groups were compared for general clinical baseline indicators. Surgical results and postoperative adverse events of patients were also compared. Disease-free survival (DFS) rate and overall survival (OS) rate was analyzed. After 1:1 PSM matching, there was no statistically significant differences in baseline data between the LCME group and D2 group (P> 0.05). LCME was characterized by longer total duration of surgery (P< 0.001), less intraoperative bleeding volume (P< 0.001), more postoperative drainage fluid volume (P< 0.001), greater number of lymph nodes retrieved (P= 0.014). No statistically differences was observed regarding intraoperative blood transfusion, hospital stay, Clavien-Dindo complicating disease classification (all P> 0.05), 1 and 3-year DFS rate (P= 0.84) and OS rate (P⩾ 0.1). LCME had a longer duration of surgery but less intraoperative bleeding volume and more postoperative drainage fluid volume and retrieved lymph nodes compared to D2 radical surgery. LCME surgery is comparable to D2 surgery in terms of postoperative prognosis, but LCME surgery shows a positive trend in the overall survival curve.

Advances in diffuse glioma assessment: preoperative and postoperative applications of chemical exchange saturation transfer.

Chemical Exchange Saturation Transfer (CEST) is a technique that uses specific off-resonance saturation pulses to pre-saturate targeted substances. This process influences the signal intensity of free water, thereby indirectly providing information about the pre-saturated substance. Among the clinical applications of CEST, Amide Proton Transfer (APT) is currently the most well-established. APT can be utilized for the preoperative grading of gliomas. Tumors with higher APTw signals generally indicate a higher likelihood of malignancy. In predicting preoperative molecular typing, APTw values are typically lower in tumors with favorable molecular phenotypes, such as isocitrate dehydrogenase (IDH) mutations, compared to IDH wild-type tumors. For differential diagnosis, the average APTw values of meningiomas are significantly lower than those of high-grade gliomas. Various APTw measurement indices assist in distinguishing central nervous system lesions with similar imaging features, such as progressive multifocal leukoencephalopathy, central nervous system lymphoma, solitary brain metastases, and glioblastoma. Regarding prognosis, APT effectively differentiates between tumor recurrence and treatment effects, and also possesses predictive capabilities for overall survival (OS) and progression-free survival (PFS).

A tumor microenvironment-activated near-infrared photosensitizer enable efficient photodynamic therapy of breast tumor

As an emerging cancer therapy with high selectivity, minimally invasive and low side effects, photodynamic therapy (PDT) has become the focus of current researches. The breast cancer is a malignant tumor with the highest incidence in women. Thus, it is valuable for improving its treatment efficiency to construct efficient photosensitizer. To this end, we engineered a high stable near-infrared photosensitizer NPA-NH2 based on “step by step” strategy. By modifying the optically tunable amino group of NPA-NH2, a peroxynitrite (ONOO-) activated NPA-ONOO- theranostic agent with a new trifluoromethylsulfonamide recognization site was designed and synthesized. It possessed a good singlet oxygen-generating ability after ONOO- activation under 660 nm light, and a high sensitivity (limit of detection: 0.038 μM) and selectivity respond toward ONOO- in buffer solution. The theranostic agent was able to specially monitor ONOO- in tumor cells. Furthermore, we have succeeded in applying the NPA-ONOO- for efficient and precise photodynamic therapy of breast cancer cells and tumors in vivo. This work provides a new way for the design of highly stable photosensitizers and a reliable tool for effective treatment of breast tumors.

Development of a UPLC-MS/MS method for quantifying KPT-335 (Verdinexor) in feline plasma for a study of PK.

KPT-335 (Verdinexor) is a novel SINE that potently inhibits the nucleoprotein Exportin 1 (XPO1/CRM1) of tumor cell lines and reduces the replication level of the influenza virus. KPT-335 is mainly used for the treatment of canine tumors. Drugs for the effective treatment of feline tumors are currently unavailable in China. KPT-335 may have potential in the treatment of cat tumors. However, the effects of KPT-335 in cats are unreported, and no relevant methodology has been established for pharmacokinetic studies. In this study, a UPLC-MS/MS method was developed to determine KPT-335 concentrations in cat plasma, followed by pharmacokinetic studies. Briefly, plasma proteins are precipitated with acetonitrile, and the supernatant was collected for detection after centrifugation. The linearity for KPT-335 in cat plasma was in the range of 5-1,000 ng/mL. Satisfactory accuracy and precision were obtained. The intra-day accuracy was between -4.10% and 10.48%, the precision was ≤4.65%; the inter-day accuracy was between -0.11% and 8.09%, and the precision was ≤5.85%. Intra-day and inter-day accuracy and precision were within regulatory limits. The results of preliminary pharmacokinetic studies were as follows: Tmax was 1.46 ± 0.51 h; Cmax was 239.54 ± 190.60 ng·mL-1; T1/2 was 5.16 ± 2.30 h; AUC0-t was 1439.85 ± 964.64 ng·mL-1·h. The AUC0-∞ was 1589.82 ± 1003.75 ng·mL-1·h. The purpose of this study was to develop a rapid and simple UPLC-MS/MS method to detect KPT-335 concentration in cat plasma and to conduct preliminary pharmacokinetic studies to support the future application of KPT-335 in felines.

Optimized Two-Photon Imaging by Stimuli-Responsive Peptide Self-Assembly Facilitates Self-Assisted Counteraction of Cisplatin-Resistance in Cancer Cells.

Accurate diagnosis and effective treatment of tumors remain significant clinical challenges. While fluorescence imaging is essential for tumor detection, it has limitations in terms of specificity, penetration depth, and emission wavelength. Here, we report a novel glutathione (GSH)-responsive peptide self-assembly excimer probe (pSE) that optimizes two-photon tumor imaging and self-assisted counteraction of the cisplatin resistance in cancer cells. The GSH-responsive self-assembly of pSE induces a monomer-excimer transition of coumarin, promoting a near-infrared redshift of fluorescence emission under two-photon excitation. This process enhances penetration depth and minimizes interference from biological autofluorescence. Moreover, the intracellular self-assembly of pSE impacts GSH homeostasis, modulates relevant signaling pathways, and significantly reduces GSTP1 expression, resulting in decreased cisplatin efflux in cisplatin-resistant cancer cells. The proposed self-assembled excimer probe not only distinguishes cancer cells from normal cells but also enhances the efficacy of cisplatin chemotherapy, offering significant potential in tumor diagnosis and overcoming cisplatin-resistant tumors.

Magnetic and pH dual responsive injectable magnetic zeolitic imidazole framework based colloidal gel for interventional treatment on hepatocellular carcinoma

Thermal ablation is frequently combined with systemic chemotherapy for treating hepatocellular carcinoma (HCC). However, the side effects of systemic chemotherapy on normal tissues limit its clinical application. Herein, we report a magnetic and pH dual-responsive colloidal gel assembled by doxorubicin (DOX)-loaded magnetic ZIF-8 and gelatin nanoparticles for HCC. The magnetic colloidal gel shows improved injectability and high functional particle loading, which could be injected through a 27G needle with an injection force as low as 8.8 N at 150 mg/mL solid content. Meanwhile, this colloidal gel could be magnetically heated and accelerated release DOX under tumor microenvironment, which presents a synergistic therapeutic effect by combining magnetic hyperthermia and localized chemotherapy. Furthermore, this colloidal gel could be manually injected interventional under ultrasound-guidance, exhibiting effective deep tumor treatment effect. Due to the high solid content, suitable injectability, and mechanical properties, the colloidal gel is also a promising embolic agent for transarterial embolization in HCC treatment.

Targeted delivery of activatable 131I-radiopharmaceutical for sustained radiotherapy with improved pharmacokinetics

Targeted radionuclide therapy (TRT) is an effective treatment for tumors. Self-condensation strategies can enhance the retention of radionuclides in tumors and enhance the anti-tumor effect. Considering legumain is overexpressed in multiple types of human cancers, a 131I-labeled radiopharmaceutical ([131I]MAAN) based on the self-condensation reaction between 2-cyanobenzothiazole (CBT) and cysteine (Cys) was developed by us recently for treating legumain-overexpressed tumors. However, liver enrichment limits its application. In this study, a new radiopharmaceutical [131I]IM(HE)3AAN was designed and synthesized by introducing a hydrophilic peptide sequence His-Glu-His-Glu-His-Glu ((HE)3) into [131I]MAAN to optimize the pharmacokinetics. Upon activation by legumain under a reducing environment, hydrophilic [131I]IM(HE)3AAN could react with its precursor to form heterologous dimer [131I]H-Dimer that is highly hydrophobic. Cerenkov imaging revealed that [131I]IM(HE)3AAN displayed superior tumor selectivity and longer tumor retention time as compared with [131I]MAAN, with a significant reduction in the liver uptake. After an 18-day treatment with [131I]IM(HE)3AAN, the tumor proliferation was obviously inhibited, while no obvious injury was observed in the normal organs. These findings suggest that [131I]IM(HE)3AAN could serve as a promising drug candidate for treating legumain-overexpressed tumors.

Dose estimation using in-beam positron emission tomography: Demonstration for 11C and 15O ion beams

Ion therapy has been well established for many decades owing to sharp depth-dose gradient and high cell-killing capability of ions. However, monitoring of the incident ions is needed to reduce ion range uncertainty for effective tumor treatment. Positron-emitting ion beams, known as radioactive ion (RI) beams, can be used as the optimal clinical approach for simultaneously treating and monitoring the incident ions using positron emission tomography (PET) imaging. The low intensity of RI beams, which previously was the main difficulty of their clinical use, was recently addressed by the development of accelerator technology. Since the quantity of interest in ion therapy is the dose and a direct comparison of planned and delivered doses is highly desirable, we focused on predicting the depth dose from PET images for RI beams in this work for the first time. We developed a method for predicting the depth dose of polyenergetic ion beams of 11C and 15O from PET images of these ion beams. The depth dose in water was measured for mono- and polyenergetic ion beams. The monoenergetic ion beams had a momentum acceptance (MA) of ±0.25%, while the polyenergetic beams had an MA of ±2.5%. PET imaging was performed during and shortly after irradiation of a polymethylmethacrylate (PMMA) phantom with mono- and polyenergetic radioactive ion beams. The energy distribution of each polyenergetic ion beam was obtained from the measured momentum distribution of that beam. A set of depth dose and PET profiles in PMMA was constructed for several monoenergetic ion beams using measured data of a monoenergetic ion beam and the range-energy relation. To estimate the depth dose for each polyenergetic beam, a linear combination of weighted PET profiles of monoenergetic beams was iteratively fitted to the measured PET profile of the polyenergetic beam, and the resulting weights were combined with the corresponding monoenergetic depth doses to predict the depth dose distribution. Significance. The depth doses of the polyenergetic ion beams were predicted with mean relative errors of 2.20% and 1.95% for 11C and 15O ion beams, respectively. These errors represent the mean value of the differences between the predicted and measured values, normalized to the maximum measured value. The predicted distal fall-off positions at 80% of the Bragg peak were within 0.13 mm of the measured values for both ion beams. The applicability of the method was demonstrated for a head phantom irradiated with 11C ion beams using Monte Carlo simulation and the predicted distal fall-off positions at 80% of the Bragg peak was within 0.08 mm of the simulated values.

A Diketopyrrolopyrrole-Based All-in-One Nanoplatform for Self-Reinforcing Mild Photothermal Therapy Cascade Immunotherapy for Tumors.

Mild photothermal therapy (PTT) has attracted attention for effectively avoiding the severe side effects associated with high-temperature tumor ablation. However, its progress is hindered by the limited availability of high-performance photothermal agents (PTAs) and the thermoresistance of cancer cells induced by heat shock reactions. Herein, this work proposes a new strategy to expand the library of high-performance organic small-molecule PTAs and utilize it to construct a multifunctional nano-theranostic platform. By incorporating additional acceptors and appropriate π-bridges, a diketopyrrolopyrrole-based dye BDB is developed, which exhibits strong absorption and bright fluorescence emission in the near-infrared (NIR)region. Subsequently, BDB is co-coated with the heat shock protein (HSP) inhibitor tanespimycin (17-AAG) using the functional amphiphilic polymers DSPE-Hyd-PEG2000-cRGD to form an all-in-one nanoplatform BAG NPs. As a result, BAG NPs can precisely target tumor tissue, guide the treatment process in real-time through NIR-II fluorescence/photoacoustic/photothermal imaging, and release 17-AAG on demand to enhance mild PTT. Additionally, the mild PTThas been demonstrated to induce immunogenic cell death (ICD) and activate a systemic anti-tumor immune response, thereby suppressing both primary and distant tumors. Overall, this study presents a multifunctional nanoplatform designed for precise mild PTT combined with immunotherapy for effective tumor treatment.

Sono-blasting Triggered Cascading-Amplification of Oxidative Stress for Enhanced Interventional Therapy of Hepatocellular Carcinoma.

Interventional therapy is widely regarded as a highly promising treatment approach for nonsurgical liver cancer. However, the development of drug resistance and tolerance to hypoxic environments after embolization can lead to increased angiogenesis, enhanced tumor cell stemness, and greater invasiveness, resulting in metastasis and recurrence. To address these challenges, a novel approach involving the use of lecithin and DSPE-PEG comodified Ca2+ loaded (NH4)2S2O8 (LDCNSO) drug in combination with transcatheter arterial embolization (TAE) has been proposed. The sono-blasting effect of LDCNSO under ultrasound triggers a cascading amplification of oxidative stress, by releasing sulfate radical (·SO4-), hydroxyl radical (·OH), and superoxide (·O2-), inducing Ca2+ overload, and reducing glutathione (GSH) levels, which eventually leads to apoptosis. LDCNSO alongside TAE has demonstrated remarkable therapeutic efficacy in the rabbit orthotopic cancer model, resulting in significant inhibition of tumor growth. This research provides valuable insights for the effective treatment of orthotopic tumors.