Tumor Therapy Research Articles

Mini‐review of developments in the chemical modification of plant‐derived photosensitizing drug hypocrellin and its biomedical applications

AbstractPhotodynamic and photothermal therapy have emerged as standard treatments for a range of tumors and microvascular diseases. However, a significant gap remains in the clinical availability of photosensitizers. Among the vast array of photosensitizers, hypocrellin–a plant‐derived photosensitizing drug–stands out as a potential candidate. It boasts straightforward preparation and purification processes, high phototoxicity, low toxicity in the absence of light, and rapid metabolism within the body. However, hypocrellin's limited water solubility and weak absorption in the phototherapeutic window pose challenges to its use in treating solid tumors. Given the limited number of reviews on this subject, a thorough investigation of hypocrellin is essential. This review focuses on the efforts of scientists to address these challenges through chemical modifications of hypocrellin and its co‐assembly with hydrophilic drug delivery vehicles. A notable advantage of hypocrellin over other photosensitizers is its amenability to modification, resulting in pure monomeric derivatives. Recent studies have shown that modifying specific functional groups on hypocrellin's parent ring can yield more potent derivatives, positioning it as a highly promising strategy in tumor therapy. Beyond its therapeutic potential, this review also explores the diverse applications of hypocrellin, including its role in bacterial and fungal inactivation, as well as its efficacy in treating malignant tumors. Additionally, the utilization of nanoparticles as carriers for modified hypocrellin presents new possibilities for clinical applications. This review offers a detailed examination of recent developments in hypocrellin modification, highlighting its potential to advance photodynamic therapy and a wider range of biomedical applications.

Piezoelectric-mediated two-dimensional copper-based metal–organic framework for synergistic sonodynamic and cuproptosis-driven tumor therapy

Sonodynamic therapy (SDT) is a minimally invasive therapeutic approach that utilizes sonosensitizers to catalyze substrates and generate reactive oxygen species (ROS) under ultrasound stimulation, ultimately inducing tumor cell death. Enhancing the piezoelectric properties of nanomaterials and modulating the semiconductor energy band are effective strategies to improve the catalytic efficiency of sonosensitizers. In this study, we developed a two-dimensional (2D) copper-based piezoelectric metal–organic framework (MOF) sonosensitizer, denoted as CM, through the coordination of copper and dimethylimidazole. The unique 2D MOF structure imparts CM with piezoelectric characteristics, enabling it to enhance SDT efficacy by modulating the semiconductor bandgap and carrier mobility. Upon ultrasound irradiation, CM catalyzes oxygen to undergo a cascade reaction, producing highly toxic singlet oxygen. Additionally, cupric ions in CM can be reduced by glutathione, facilitating the spontaneous catalysis of hydrogen peroxide in tumors to generate hydroxyl radicals and deplete glutathione, thereby inducing oxidative damage. Moreover, cupric ions in CM can trigger tumor cell cuproptosis, which, in combination with the generated ROS, accelerates cell death. Thus, this study establishes a MOF-based system for controllably inducing multi-pathway cancer cell death and provides a foundation for enhancing ultrasound-catalyzed tumor therapy through the optimization of piezoelectric properties.

Exosome-decorated bio-heterojunctions reduce heat and ROS transfer distance for boosted antibacterial and tumor therapy

Photothermal and photodynamic therapies represent effective modalities for combatting bacteria and tumor cells. However, therapeutic outcomes are constrained by limitations related to the heat and reactive oxygen species (ROS) transfer distance from photosensitizers to targets. To address this issue, we have devised and developed exosome-decorated bio-heterojunctions (E-bioHJ) consisted of MXene (Ti3C2), liquid metal (LM) and exosomes sourced from CT26 cells to enhance the phototherapeutic consequences. Engineering E-bioHJ enhances phototherapeutic effect in antibacterial and anti-tumor treatment, which is ascribed to reducing transfer distance of the heat and ROS. When adorned with exosomes, E-bioHJ is targetedly delivered into the cytoplasm of tumor cells to generate amount heat and ROS under 808 nm near-infrared radiation, which further induces mitochondrial dysfunction and apoptosis/necroptosis. As envisaged, this study presents a novel tactic to enhance the antibacterial and anti-tumor efficacy of biomaterials through reducing the heat and ROS delivery travel distance.

Targeting senescence with radioactive 223Ra/Ba SAzymes enables senolytics-unlocked One‐Two punch strategy to boost anti-tumor immunotherapy

Senescent cells are characterized by a persistent cessation of their cell cycle, rendering them valuable targets for anti-tumor strategies in cancer treatment. Numerous studies have explored induced senescence as a promising approach in tumor therapy. Nevertheless, these treatments often come with drawbacks, including adverse side effects and weaker senescence-inducing effects. To address these challenges, we synthesized 223Ra/Ba single-atom nanozyme (SAzyme), wherein Ba SAzyme acts concurrently as a carrier for 223RaCl2, facilitating targeted delivery and minimizing side effects. The 223Ra/Ba SAzyme complex enhances various enzyme-mimicking functions, including catalase (CAT) and peroxidase (POD) activities. Importantly, 223Ra/Ba SAzyme induces cellular senescence and boost anti-tumor immunity. The persistent presence of a senescence-associated secretory phenotype (SASP) in the tumor microenvironment presents risks of immune suppression and tumor recurrence, which can be effectively mitigated by senolytics. As a result, 223Ra/Ba SAzyme were combined with anti-PD-L1 checkpoint blockade to achieve a one-two punch therapy, wherein 223Ra/Ba SAzyme exploits senescence followed by anti-PD-L1 therapy to eradicate senescent cells. This one‐two punch strategy approach presents a straightforward and potent intervention for both primary tumors and distant tumor.

CAR-redirected natural killer T cells demonstrate superior antitumor activity to CAR-T cells through multimodal CD1d-dependent mechanisms.

Human natural killer T (NKT) cells have been proposed as a promising cell platform for chimeric antigen receptor (CAR) therapy in solid tumors. Here we generated murine CAR-NKT cells and compared them with CAR-T cells in immune-competent mice. Both CAR-NKT cells and CAR-T cells showed similar antitumor effects in vitro, but CAR-NKT cells showed superior antitumor activity in vivo via CD1d-dependent immune responses in the tumor microenvironment. Specifically, we show that CAR-NKT cells eliminate CD1d-expressing M2-like macrophages. In addition, CAR-NKT cells promote epitope spreading and activation of endogenous T cell responses against tumor-associated neoantigens. Finally, we observed that CAR-NKT cells can co-express PD1 and TIM3 and show an exhaustion phenotype in a model of high tumor burden. PD1 blockade as well as vaccination augmented the antitumor activity of CAR-NKT cells. In summary, our results demonstrate the multimodal function of CAR-NKT cells in solid tumors, further supporting the rationale for developing CAR-NKT therapies in the clinic.

Inhibitory Fcγ receptor deletion enhances CD8 T cell stemness increasing anti-PD-1 therapy responsiveness against glioblastoma

BackgroundCertain cancers present challenges for treatment because they are resistant to immune checkpoint blockade (ICB), attributed to low tumor mutational burden and the absence of T cell-inflamed features. Among these,...

Oncogenic Mutant p53 Sensitizes Non-Small Cell Lung Cancer Cells to Proteasome Inhibition via Oxidative Stress-Dependent Induction of Mitochondrial Apoptosis.

NSCLC is the leading cause of cancer death due, in part, to a lack of active therapies in advanced disease. We demonstrate that combination therapy with a proteasome inhibitor, BH3-mimetic, and chemotherapy is an active precision therapy in NSCLC cells and tumors expressing Onc-p53 alleles.

Assessment of different shielding materials for radiation therapy of maxillofacial tumors – An in vitro study

Aim: Since the advent of radiotherapy, the success rate of head and neck cancer treatment has increased significantly. However, when the tissue tolerance level is exceeded, unnecessary and uncontrolled exposure to radiation is considered detrimental. Such problems remain difficult to prevent and manage. The aim of the study to evaluate and compare the degree of attenuation of therapeutic radiation using four different radiation shielding materials of varying thickness. Study Setting and Design: In vitro experimental study. Materials and Methods: The samples were divided into four groups based on the different radiation shielding materials of thickness 3mm and 5mm. The materials are Lead (Pb), Silver-tin alloy (Ag-Sn) with Polyvinylsiloxane (PVS), Polymethylmethacrylate (PMMA) with Barium sulphate (BaSO4), and a combination of Ag-Sn with PVS and PMMA with BaSO4 which was exposed to radiation. The radiation dose measurements were recorded and the radiation attenuation properties of the shielding materials were evaluated. Among all of the shielding materials the most efficient material under consideration is determined. Statistical Analysis Used: One-way ANOVA followed by post hoc test was used to compare the means of all four groups. Results: A statistically significant difference between groups was found by a one-way ANOVA with a P = 0.001. In the post hoc test, statistically significant findings were obtained with a P = 0.05 when comparing the variation values of 3mm and 5mm thickness between each group and other groups. Conclusion: The shielding materials results in significant reductions in radiation dosage. It was concluded that the combinations of Ag-Sn alloy with PVS, and PMMA with BaSO4 of thickness 5 mm had a good shielding effect.

Patient reported fatigue after proton therapy for malignant brain tumours – Is there a relation between radiation dose and brain structures?

BackgroundFatigue may significantly effect everyday- and working life for radiotherapy patients. Some studies indicate a correlation between radiation dose and irradiated volume of the brain and the presence of fatigue. Our hypothesis was that patient reported outcome measures (PROMs) can improve our understanding of the patients’ symptoms following proton beam therapy (PBT) and optimize PBT for future patients. MethodsThis study included 167 adult patients (>18 years) who received PBT for malignant brain tumours. Data on dose metrics to intra-cranial structures was obtained from PBT treatment plans. To explore fatigue and health related quality of life (HRQoL); Multidimensional Fatigue Inventory (MFI-20) and EORTC QLQ-C30 was used at 6-, 12-, 24- and 36 months post PBT. The correlation between fatigue and dosimetry was explored using Spearman’s signed rank test. ResultsNo severe fatigue was recorded during the 36 months follow-up. Correlations between higher radiation dose and worsened fatigue scores were generally weak (rho < 0.3). At 12 months post PBT, higher mean dose to the brain, brainstem, hippocampi and pituitary was correlated to worsened MFI Physical Fatigue. Further, Reduced Motivation according to MFI was correlated to higher radiation dose to the brainstem and the pituitary gland. At 36 months follow-up post-PBT, both Reduced Activity and Reduced motivation according to MFI were correlated to higher radiation dose to the brain, brainstem and hippocampi. ConclusionProton beam therapy are well tolerated, with similar degree of fatigue pre- and post PBT. Achieving further reduction in mean brain dose appears beneficial.

Alleviating tumor hypoxia and immunosuppression via sononeoperfusion: A new Ally for potentiating anti-PD-L1 blockade of solid tumor

The hypoxic and immunosuppressive tumor microenvironment (TME) remains a major obstacle to impede cancer immunotherapy. Here, we found that sononeoperfusion—a new effect of tumor perfusion enhancement induced by low mechanical index ultrasound stimulated microbubble cavitation (USMC)—ameliorated tumor tissue oxygenation and induced tumor vascular normalization (TVN). This TVN might be associated with the down-regulation of hypoxia-inducible factor 1-alpha (HIF-1α) and vascular endothelial growth factor (VEGF) within tumors. Moreover, the sononeoperfusion effect reduced the accumulation of immunosuppressive cells, such as regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and M2-like tumor-associated macrophages (M2-TAMs), and decreased the production of immune inhibitory factors like transforming growth factor-β1 (TGF-β1), interleukin 10 (IL-10), chemoattractant chemokines CC-chemokine ligand 22 (CCL22), CCL28, adenosine and lactate within tumors. Notably, flow cytometry analysis revealed that sononeoperfusion not only increased the percentage of tumor infiltrating-CD8+ T cells, but also promoted the generation of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) by these cells. Furthermore, the improved immune TME by sononeoperfusion effect sensitized anti-PD-L1 treatment both in MC38 colon cancer and Lewis lung carcinoma mice, resulting in tumor regression and prolonged survival. Mechanically, the enhanced efficacy of combination therapy was mainly based on promoting the infiltration and function of CD8+ T cells within tumors. Together, sononeoperfusion could ameliorate hypoxia and immunosuppression in the TME, thereby potentiating anti-PD-L1 therapy for solid tumors. This novel method of USMC generating sononeoperfusion effect may provide a new therapeutic modality for facilitating cancer immunotherapy.

Efficacy of iodized oil in emergency ultraselective arterial embolization for fatal massive hemorrhage due to renal angiomyolipoma: a single-center retrospective cohort study.

In recent years, the area of minimally invasive, targeted therapy for kidney tumors has seen considerable advancement; however, little progress has been made in the evaluation of renal angiomyolipoma (RAML). We aimed to investigate the efficacy of emergency ultraselective arterial embolization for the treatment of fatal massive bleeding caused by RAML. At The First Hospital of Jilin University, a retrospective study was conducted between January 1, 2019 and March 1, 2024. The enrolled patients were those experiencing intense flank pain with a ruptured RAML and hemorrhage as confirmed through computed tomography (CT) and magnetic resonance imaging (MRI) in the emergency department. We performed renal arteriography and vascular ultraselective embolization in patients with ruptured and bleeding RAML. Patient information, including age, sex, tumor size, embolic material, several blood laboratory parameters, and postembolization syndrome (PES) occurrence, was retrospectively analyzed. PES was defined as the occurrence of fever, pain, nausea, or vomiting. This study ultimately enrolled 27 patients. After emergency embolization, 27 patients had 100% stable red blood cells and hemoglobin, and 7 patients had a single lesion and underwent surgical resection after the bleeding was stabilized. After emergency embolization, 22 patients experienced relief of low back pain as compared to pretreatment conditions, and the rate of lower back pain relief was 81.48%. Significantly higher creatinine and urea nitrogen levels were observed in three patients prior to the operation, and these levels reverted to their original state after renal function protection therapy. Despite varying levels of PES, all of the patients' symptoms returned to their normal levels following symptomatic treatment, with no significant impact on their quality of life or recovery period. Emergency ultraselective arterial embolization for the treatment of bleeding in fatal RAML is safe, rapid, and effective and has few complications. The use of iodized oil can not only serve an embolic function but also provide a tracer effect in subsequent reexamination.

Immune-related and common adverse events with PD-1/PD-L1 inhibitors combined with other anticancer therapy for solid tumors: a systematic review and meta-analysis

AimsThe combination of programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) inhibitors and anticancer therapies has been in the spotlight in recent years. However, the risks associated with these combination therapies are not fully elucidated. The primary objective of this study was to evaluate the relative risk of organ-specific immune-related adverse events (irAEs) and common adverse events (AEs) in patients treated with PD-1/PD-L1 inhibitor-based combination therapies compared to those treated with PD-1/PD-L1 inhibitor monotherapy for solid tumors. Materials and methodsAn electronic database search was performed using ClinicalTrials.gov, Medline, and ASCO/ESMO Annual Meeting Libraries. We included randomized controlled trials designed to assess the safety of combination therapies using PD-1/PD-L1 inhibitors and other anticancer drugs. All the selected clinical studies included solid tumors and provided information on the incidence of non-serious and serious AEs. The quality of evidence was assessed using the Cochrane risk-of-bias tool. A meta-analysis was performed using random effects models to pool the results. ResultsThe primary analysis included 16 relevant clinical studies comprising 4232 patients, of whom 2071 and 2161 patients received PD-1/PD-L1 inhibitor-based combination therapy, and PD-1/PD-L1 inhibitor monotherapy, respectively. Serious organ-specific irAEs were infrequent, even when PD-1/PD-L1 inhibitors were combined with other anticancer drugs. The incidence of serious colitis was significantly higher in the combination therapy group than in the monotherapy group. Among the common AEs associated with PD-1/PD-L1 inhibitors, the incidence of serious pyrexia/fever, non-serious pyrexia/fever, fatigue, nausea, decreased appetite, vomiting, diarrhea, dyspnea, and rash significantly increased in the combination therapy group. In the subgroup analysis based on the modes of action of concomitant anticancer drugs, the combination of PD-1/PD-L1 inhibitors and DNA synthesis inhibitors significantly increased the risk of serious colitis compared to PD-1/PD-L1 inhibitor monotherapy. ConclusionOrgan-specific irAEs occur infrequently when combinations of PD-1/PD-L1 inhibitors and other anticancer drugs are used. However, the risk of serious colitis and certain AEs is higher than that associated with PD-1/PD-L1 inhibitor monotherapy. Vigilant monitoring of AEs and implementation of appropriate clinical management strategies guided by the mode of action of the combination drugs are essential. ProsperoRegistration number CRD42022379088.

DKN-01 Suppresses Gastric Cancer Progression Through Activating cGAS-STING Pathway to Block Macrophage M2 Polarization.

Dickkopf-1 (DKK1) is a secretory antagonist that can bind with the Wnt coreceptor to desensitize cells to canonical Wnt ligands. DKN-01 is a specific antibody targeting secreted DKK1, which has been investigated as a monotherapy or combination therapy for various malignant tumors, including gastric cancer (GC). Tumor-associated macrophages (TAMs) with high plasticity usually present M2 phenotype, which can promote tumor progression. The aim of this study was to investigate the effect of DKN-01 on macrophage polarization in GC and the underlying molecular mechanism. To ascertain the effect of DKN-01 on GC tumor growth, we established a tumor-bearing mouse model and found that DKN-01 treatment suppressed tumor growth efficiently. Through RNA-seq and pathway enrichment analysis, we identified that the differentially expressed genes after DKN-01 treatment are associated with tumor immune-related pathways. Macrophage polarization was assessed using immunohistochemistry and quantitative real-time polymerase chain reaction. DKN-01 and knockdown of DKK1 promoted M1 polarization and inhibited M2 polarization of macrophages, while DKK1 overexpression got the opposite results. Moreover, DKN-01 activated the cGAS/STING pathway, while the inactivation of cGAS-STING pathway using RU.521 reversed the inhibition of tumor growth in vivo and macrophage M2 polarization caused by DKN-01. This study reveals that DKN-01 suppresses GC tumor growth through activating cGAS-STING pathway to block macrophage M2 polarization.

Dual targeting macrophages and microglia is a therapeutic vulnerability in models of PTEN-deficient glioblastoma.

Tumor-associated macrophages and microglia (TAMs) are critical for tumor progression and therapy resistance in glioblastoma (GBM), a type of incurable brain cancer. We previously identified lysyl oxidase (LOX) and olfactomedin like-3 (OLFML3) as essential macrophage and microglia chemokines, respectively, in GBM. Here, single-cell transcriptomics and multiplex sequential immunofluorescence followed by functional studies demonstrate that macrophages negatively correlate with microglia in the GBM tumor microenvironment. LOX inhibition in PTEN-deficient GBM cells upregulates OLFML3 expression via the NF-κB-PATZ1 signaling pathway, inducing a compensatory increase of microglia infiltration. Dual targeting macrophages and microglia via inhibition of LOX and the CLOCK-OLFML3 axis generates potent anti-tumor effects and offers a complete tumor regression in more than 60% of animals when combined with anti-PD1 therapy in PTEN-deficient GBM mouse models. Thus, our findings provide a translational triple therapeutic strategy for this lethal disease.

Arterial prophylactic occlusion technique in the application of surgery for locally advanced pancreatic cancer with arterial involvement after conversion therapy

Objective: To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy. Methods: This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher's exact test were used to compare the data between the two groups,respectively. Results: After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant (t=-3.800,P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml;U=1 026.500,P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups(P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups(P=0.532,P=0.927). Conclusion: The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.

Photovoltaic Molecule-Based Phototheranostics With A-D-A Structure for Near-Infrared Fluorescence Imaging-Guided Synergetic Photodynamic and Photothermal Therapy of Tumors.

Phototheranostics with near-infrared fluorescence and reactive oxygen species generation ability and high photothermal conversion efficiency (PCE) plays a significant role in fluorescence imaging-guided synergetic photodynamic and photothermal therapy of tumors. Here, a star molecule in organic photovoltaic materials, NCBDT-4C with an A-D-A conjugated structure, was assembled with DSPE-PEG-NH2 to prepare water dispersive nanoparticles (NPs). The prepared NCBDT-4Cl NPs exhibited a maximum NIR absorption peak at 764 nm and a maximum fluorescence peak at 798 nm. These NPs could generate superoxide anion, singlet oxygen (1O2), and heat under 808 nm laser irradiation. The 1O2 generation quantum yield and PCE of the NPs were 37.5% and 53.6%, respectively. The combination of photodynamic and photothermal therapy of cancer was demonstrated invitro and invivo. This work presents the advanced application of organic photovoltaic materials in cancer phototherapy.

Bovine serum albumin framed activatable NIR AIE photosensitizer for targeted tumor therapy

Organic near-infrared (NIR) photosensitizers (PS) largely facilitate photodynamic therapy (PDT). To overcome aggregation induced quenching and diminishment of reactive oxygen species (ROS) generation capability of NIR-PS, aggregation-induced emission (AIE) effect groups have been introduced to generate NIR AIE photosensitizers. However, currently reported NIR AIE photosensitizers all take “always-on” activity that may cause systemic phototoxic side effects. Tumor microenvironment activatable NIR AIE photosensitizers have not been reported. Here we develop an activatable NIR AIE PS nanoparticle (a-NA-PSNP) for near-infrared-II (NIR-II) fluorescence (FL) imaging-guided PDT under 808 nm excitation. NIR AIE photosensitizer (N-PS) is designed and frames with cysteine (Cys)/glutathione (GSH) responsive charge transfer complex (CTC) in bovine serum albumin (BSA) to obtain a-NA-PSNP. With the aggregated state in BSA, N-PS shows high quantum yield with good photostability. As an energy acceptor, CTC quenchs NIR-II fluorescence and ROS production capability of a-NA-PSNP in normal cells and tissues. CTC is decomposed in response to tumor microenvironment Cys/GSH, therefore recovers NIR-II fluorescence of a-NA-PSNP and efficiently generates ROS under 808 nm light irradiation. The depletion of Cys/GSH also regulates tumor intracellular reductive environment to further facilitate PDT. Both in vitro and in vivo results confirmed the tumor microenvironment selective and efficient activation of a-NA-PSNP, indicating its potential in cancer therapy.

410 (PB398): Optimizing metastatic tumor therapies: innovative drug screening using colonies derived from circulating tumor cells

410 (PB398): Optimizing metastatic tumor therapies: innovative drug screening using colonies derived from circulating tumor cells

A computation analysis with heat and mass transfer for micropolar nanofluid in ciliated microchannel: With application in the ductus efferentes

Inherited heat enhancement capabilities and their significance in the field of medical sciences and industry make nanofluids the focus of research nowadays. Furthermore, due to the remarkable advancements in bionanotechnology and its significance in biomedical fields such as drug delivery systems, cancer tumor therapy, bioimaging, and many others, it has emerged as a key research area. Contribution of cilia for the flow in ductus efferentes of human male reproductive tract is elaborated. A novel mathematical scheme is presented for the heat and mass transfer of MHD micropolar nanofluid transport in an asymmetric channel lined with cilia. The pertinent equations of nanofluid transport are exposed to lubrication approximation theory and solution for the physical problem is examined with efficient bvp4c technique in MATLAB. Fluid rheology is explored with the variations of different transport parameters like Hartmann number, Grashof number, Brownian motion, buoyancy, thermophoresis and Darcy number. It is reported that nanofluid transport is affected with rise in the Lorentz force and show reverse behavior with rising permeability. The temperature of the nanofluid in ciliated microchannel is raised with enhanced value of Hartmann number, Grashof number, Prandtl number, and Darcy number while diffusion phenomenon of nanofluid is slowed down with these parameters. Spinning motion of the nanofluid is enhanced with Grashof number and slow down with nanoparticle Grashof number and different behavior is recorded for Darcy and viscosity parameters in different flow regime. Reported investigation presents crucial findings for ciliary transport of micropolar nanofluid and tackled with appropriate selection of micropolar parameter, Brownian motion parameter, thermophoresis and Grashof number. Moreover, this investigation will be handful for cilia-based actuators which work as micro-mixers in controlling the flow in minute bio-sensors and may prove their worth in micro-pumps employed in various drug-delivery systems.

Exploration and application of treating OSCC by a precisely concentrated synergistic agent in combination with thermally responsive release of effective therapeutic dosages of cisplatin

Platinum-based drugs, foremost among them Cisplatin (CDDP), currently constitute the primary line of chemotherapy for the treatment of oral squamous cell carcinoma (OSCC). However, the extensive utilization of these drugs often results in undesirable systemic toxic side effects. Consequently, in clinical practice, emphasis has shifted towards the adoption of combination drug strategies, aimed at minimizing the dosage of platinum-based drugs while preserving optimal anti-tumor efficacy. Prior research has concentrated on the co-loading of drugs with synergistic potential into a unified nanosystem, yet this approach does not guarantee that the drugs will remain within the concentration range necessary for synergistic effects following nanocarrier release, thus limiting the full exploitation of their synergistic anti-tumor properties. This study has pioneered the discovery that the HSP90 inhibitor 17AAG exhibits remarkable synergistic effects with CDDP in the treatment of OSCC. Importantly, 17AAG can allow CDDP to still exert effective tumor killing effects at lower concentrations. Furthermore, specific concentrations of 17AAG demonstrate synergistic effects with a wide range of CDDP concentrations, positioning it as a promising candidate for the sustained synergistic augmentation of CDDP released from nanocarriers. Additionally, we have augmented CDDP targeting through the employment of a hybrid membrane strategy, encapsulating CDDP and photosensitizers concurrently. This approach enhances CDDP’s targeting precision and enables responsive tracking and release. Notably, we have observed that altering the tumor cell membrane type significantly modifies the tumor targeting profile of the hybrid membrane, suggesting that cell membrane-modified nanocarriers have potential value in achieving personalized tumor therapy. In summary, we have formulated a novel CDDP-based targeted therapy strategy for OSCC, which holds promising implications for future treatment of this malignancy.