A Photodynamic and Photochemotherapeutic Platinum-Iridium Charge-Transfer Conjugate for Anticancer Therapy.

The novel hetero-dinuclear complex trans,trans,trans-[PtIV(py)2(N3)2(OH)(µ-OOCCH2CH2CONHCH2-bpyMe)IrIII(ppy)2]Cl (Pt-Ir), exhibits charge transfer between the acceptor photochemotherapeutic Pt(IV) (Pt-OH) and donor photodynamic Ir(III) (Ir-NH2) fragments. It is stable in the dark, but undergoes photodecomposition more rapidly than the Pt(IV) parent complex (Pt-OH) to generate Pt(II) species, an azidyl radical and 1O2. The Ir(III)* excited state, formed after irradiation, can oxidise NADH to NAD⋅ radicals and NAD+. Pt-Ir is highly photocytotoxic towards cancer cells with a high photocytotoxicity index upon irradiation with blue light (465 nm, 4.8 mW/cm2), even with short light-exposure times (10-60 min). In contrast, the mononuclear Pt-OH and Ir-NH2 subunits and their simple mixture are much less potent. Cellular Pt accumulation was higher for Pt-Ir compared to Pt-OH. Irradiation of Pt-Ir in cancer cells damages nuclei and releases chromosomes. Synchrotron-XRF revealed ca. 4× higher levels of intracellular platinum compared to iridium in Pt-Ir treated cells under dark conditions. Luminescent Pt-Ir distributes over the whole cell and generates ROS and 1O2 within 1 h of irradiation. Iridium localises strongly in small compartments, suggestive of complex cleavage and excretion via recycling vesicles (e.g. lysosomes). The combination of PDT and PACT motifs in one molecule, provides Pt-Ir with a novel strategy for multimodal phototherapy.

Biosynthesis of palladium, platinum, and their bimetallic nanoparticles using rosemary and ginseng herbal plants: evaluation of anticancer activity.

In this research, palladium (II) and platinum (II), as well as their bimetallic nanoparticles were synthesized using medicinal plants in an eco-friendly manner. Rosemary and Ginseng extracts were chosen due to their promising anticancer potential. The synthesized nanoparticles underwent characterization through FT-IR spectroscopy, DLS, XRD, EDX, SEM, and TEM techniques. Once the expected structures were confirmed, the performance of these nanoparticles, which exhibited an optimal size, was evaluated as potential anticancer agents through in vitro method on colon cancer cell lines (Ls180, SW480). MTT assay studies showed that the synthesized nanoparticles induced cell death. Moreover, real-time PCR was employed to investigate autophagy markers and the effect of nanoparticles on the apoptosis process, demonstrating a significant effect of the synthesized compounds in this regard.

Pt,P-codoped carbon nitride nanoenzymes for fluorescence and colorimetric dual-mode detection of cholesterol.

Cholesterol is an important lipid compound found in a variety of foods, and its level in human blood is closely related to human health. Therefore, development of rapid and accurate POCT (point-of-care testing) methods for cholesterol detection is crucial for assessing food quality and early diagnosis of diseases, in particular, in a resource-limited environment. In this study, a smartphone-assisted colorimetric biosensor is constructed based on platinum,phosphorus-codoped carbon nitride (PtCNP2) for the rapid detection of cholesterol. Phosphorus-doped carbon nitride is prepared by thermal annealing of urea and NH4PF6, into which platinum is atomically dispersed by thermal refluxing. The obtained PtCNP2 exhibits an excellent peroxidase-like activity under physiological pH, whereby colorless o-phenylenediamine (OPD) is oxidized to colored 2,3-diaminophenazine (DAP) in the presence of hydrogen peroxide (H2O2), which can be produced during the oxidation of cholesterol by cholesterol oxidase. A smartphone-assisted visual sensing system is then constructed based on the color recognition software, and rapid on-site detection of cholesterol is achieved by reading the RGB values. Meanwhile, the generated DAP shows an apparent fluorescence signal and can realize highly sensitive detection of cholesterol by the change of the fluorescence signal intensity. Such a cholesterol sensor exhibits a wide linear detection range of 0.5-600 µg mL-1 and a low detection limit of 59 ng mL-1. The practicality of the sensor is successfully demonstrated in the rapid detection of cholesterol in serum and food.

Glomerular filtration rate measurement during platinum treatment for urothelial carcinoma: optimal methods for clinical practice.

BACKGROUND: We assessed the accuracy of four estimated glomerular filtration rate (eGFR) methods: MDRD, Cockcroft-Gault, CKD-EPI, and Wright. METHOD: The four methods were compared to measure GFR (mGFR) in patients with urothelial urinary tract cancer (T2-T4bNxMx) receiving platinum-based chemotherapy at Rigshospitalet, Copenhagen, from January 2019 to December 2021. Using standardized assays, creatinine values were measured, and mGFR was determined using Technetium-99 m diethylenetriaminepentaacetic acid (Tc-99 m-DTPA) or Cr-51-ethylenediaminetetraacetic acid (Cr-51-EDTA) plasma clearance. Patients (n = 146) with both mGFR and corresponding creatinine values available were included (n = 345 measurements). RESULTS: The CKD-EPI method consistently demonstrated superior accuracy, with the lowest Total Deviation Index of 21.8% at baseline and 22.9% for all measurements compared to Wright (23.4% /24.1%), MDRD (26.2%/25.5%), and Cockcroft-Gault (25.x%/25.1%). Bland Altman Limits of agreement (LOA) ranged from - 32 ml/min (Cockcroft-Gault) to + 33 ml/min (MDRD), with CKD-EPI showing the narrowest LOA (- 27 ml/min to + 24 ml/min and lowest bias (0.3 ml/min). Establishing an eGFR threshold at 85 ml/min-considering both the lower limit of agreement (LOA) and the minimum cisplatin limit at 60 ml/min-allows for the safe omission of mGFR in 30% of patients in this cohort. CONCLUSION: CKD-EPI equation emerged as the most suitable for estimating kidney function in this patient group although not meeting benchmark criteria. We recommend its use for initial assessment and ongoing monitoring, and suggest mGFR for patients with a CKD-EPI estimated GFR below 85 ml/min. This approach could reduce costs and decrease laboratory time for 30% of our UC patients.

Adjuvant platinum versus capecitabine for residual, invasive, triple-negative breast cancer: Patient-reported outcomes in ECOG-ACRIN EA1131.

BACKGROUND: Patient-reported outcomes (PROs) are a better tool for evaluating the experiences of patients who have symptomatic, treatment-associated adverse events (AEs) compared with clinician-rated AEs. The authors present PROs assessing health-related quality of life (HRQoL) and treatment-related neurotoxicity for adjuvant capecitabine versus platinum on the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network (ECOG-ACRIN) EA1131 trial (ClinicalTrials.gov identifier NCT02445391). METHODS: Participants completed the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (NFBSI-16) and the Functional Assessment of Cancer Therapy-Gynecologic Oncology Group neurotoxicity subscale (platinum arm only) at baseline, cycle 3 day 1 (C3D1), 6 months, and 15 months. Because of early termination, power was insufficient to test the hypothesis that HRQoL, as assessed by the NFBSI-16 treatment side-effect (TSE) subscale, would be better at 6 and 15 months in the capecitabine arm; all analyses were exploratory. Means were compared by using t-tests or the Wilcoxon rank-sum test, and proportions were compared by using the χ2 test. RESULTS: Two hundred ninety-six of 330 eligible patients provided PROs. The mean NFBSI-16 TSE subscale score was lower for the platinum arm at baseline (p = .02; absolute difference, 0.6 points) and for the capecitabine arm at C3D1 (p = .04; absolute difference, 0.5 points), but it did not differ at other times. The mean change in TSE subscale scores differed between the arms from baseline to C3D1 (platinum arm, 0.15; capecitabine arm, -0.72; p = .03), but not from baseline to later time points. The mean decline in Functional Assessment of Cancer Therapy-Gynecologic Oncology Group neurotoxicity subscale scores exceeded the minimal meaningful change (1.38 points) from baseline to each subsequent time point (all p < .05). CONCLUSIONS: Despite the similar frequency of clinician-rated AEs, PROs identified greater on-treatment symptom burden with capecitabine and complemented clinician-rated AEs by characterizing patients' experiences during chemotherapy.

Amphiphilic polymeric nanodrug integrated with superparamagnetic iron oxide nanoparticles for synergistic antibacterial and antitumor therapy of colorectal cancer.

Colorectal cancer (CRC) is one of the most prevalent and deadly malignancies that can be influenced by Fusobacterium nucleatum (Fn), a bacterium that promotes tumor development and chemoresistance, resulting in limited therapeutic efficacy. Traditional antibiotics cannot effectively eliminate Fn at tumor site due to issues like biofilm formation, while chemotherapy alone fails to suppress tumor progression. Therefore, the development of new methods to eliminate Fn and promote antitumor efficacy is of great significance for improving the outcome of CRC treatment. Herein, we developed a nanodrug (OPPL) that integrates oleic acid-modified superparamagnetic iron oxide nanoparticles (O-SPIONs) and an amphiphilic polymer (PPL) to deliver the platinum prodrug and antimicrobial lauric acid (LA) for enhancing the treatment of CRC. We demonstrated that OPPL can synergistically enhance antibacterial and biofilm disruption activities against Fn along with the antimicrobial LA by producing reactive oxygen species (ROS) through its peroxidase-like activity. Furthermore, the OPPL nanodrug can increase intracellular ROS, promote lipid peroxides and deplete glutathione, leading to ferroptosis. By combining chemotherapy and induced ferroptosis, the OPPL nanodrug exhibited high cytotoxicity against CRC cells. In vivo studies showed that the OPPL nanodrug could enhance tumor accumulation, enable magnetic resonance imaging, suppresse tumor growth, and inhibit growth of intratumor Fn. These results suggest that OPPL is an effective and promising candidate for the treatment of Fn-infected CRC. STATEMENT OF SIGNIFICANCE: The enrichment of Fusobacterium nucleatum (Fn) in colorectal cancer is reported to exacerbate tumor malignancy and is particularly responsible for chemoresistance. To this respect, we strategically elaborated multifaceted therapeutics, namely OPPL nanodrug, combining oleic acid-modified superparamagnetic iron oxide nanoparticles (O-SPIONs) with a polymer containing a platinum prodrug and antimicrobial lauric acid. The O-SPION components exert distinctive peroxidase-like activity, capable of stimulating Fenton reactions selectively in the tumor microenvironment, consequently accounting for the progressive production of reactive oxygen species. Hence, O-SPIONs have been demonstrated to not only supplement the antimicrobial activities of lauric acid in overcoming Fn-induced chemoresistance but also stimulate potent tumor ferroptosis. Our proposed dual antimicrobial and chemotherapeutic nanodrug provides an appreciable strategy for managing challenging Fn-infected colorectal cancer.

A Pt1Pd Single-Atom Alloy Nanozyme with Boosted Enzyme-Like Activity for Efficient Photo-Mediated Tumor Therapy.

Single-atom nanozymes (SAzymes) are emerging natural enzyme mimics and have attracted much attention in the biomedical field. SAzymes with Metal─Nx sites designed on carbon matrixes are currently the mainstream in research. It is of great significance to further expand the types of SAzymes to enrich the nanozyme library. Single-atom alloys (SAAs) are a material in which single-atom metal sites are dispersed onto another active metal matrix, and currently, there is limited research on their enzyme-like catalytic performance. In this work, a biodegradable Pt1Pd SAA is fabricated via a simple galvanic replacement strategy, and for the first time reveals its intrinsic enzyme-like catalytic performance including catalase-, oxidase-, and peroxidase-like activities, as well as its photodynamic effect. Experimental characterizations demonstrate that the introduction of single-atom Pt sites contributes to enhancing the affinity of Pt1Pd single-atom alloy nanozyme (SAAzyme) toward substrates, thus exhibiting boosted catalytic efficiency. In vitro and in vivo experiments demonstrate that Pt1Pd SAAzyme exhibits a photo-controlled therapeutic effect, with a tumor inhibition rate of up to 100%. This work provides vital guidance for opening the research direction of SAAs in enzyme-like catalysis.

The effect of selenium yeast in the prevention of adverse reactions related to platinum-based combination therapy in patients with malignant tumors.

OBJECTIVE: The aim of this was study was to analyze the effect of selenium yeast in the prevention of adverse reactions related to platinum-based combination therapy in patients with malignant tumors. PATIENTS AND METHODS: A total of 86 patients with malignant tumors treated in Anhui No. 2 Provincial People's Hospital were randomized to receive either platinum-containing combined regimen with selenium yeast at a dose of 200 ug daily (observation group) or platinum-containing combined regimen without selenium yeast (control group), with 43 cases in each group. RESULTS: The platinum-containing combined regimen exhibited similar total effectiveness either with (25.58%) or without selenium yeast (23.26%) (p>0.05). Patients with selenium yeast treatment after chemotherapy had better appetites and more stable body weights than those without selenium yeast (p<0.05). The platinum-containing combined regimen significantly improved the quality of life of the patients, as evidenced by the elevated Karnofsky Performance Status (KPS) scores of the two groups, and selenium yeast treatment potentiated this improvement (p<0.05). Selenium yeast treatment significantly reduced the incidence of adverse reactions in patients after chemotherapy by 23.26% (p<0.05), and patients also experienced milder adverse reactions after selenium yeast administration (z=-2.438, p=0.015). Chemotherapy with selenium yeast treatment provided better pain mitigation for patients vs. without selenium yeast administration (Z=0.854, p=0.041 <0.05). CONCLUSIONS: In the clinical treatment of patients with malignant tumors, a 200 ug dose of selenium yeast significantly reduced the adverse reactions related to chemotherapy, improved the patient's post-chemotherapy appetite, prevented weight loss, and provided significant pain mitigation. Therefore, selenium yeast may offer a viable alternative for the management of cancer patients undergoing chemotherapy to enhance treatment effectiveness and reduce adverse events in clinical practice.

In stage IV pulmonary adenocarcinoma patients, treatment with Traditional Chinese Medicine alone gives prognostically superior results to treatment with Platinum-Based Chemotherapy alone.

BACKGROUND: About 30% of pulmonary stage IV adenocarcinomas die within 3 months of diagnosis. Western medical treatments with Platinum-Based Chemotherapy=PBC and tyrosine-kinase inhibitors Targeted Therapy=TT can improve prognosis. In China, Traditional Chinese Medicine herbal treatments (TCM) are often used in addition to PBC and TT. A considerable number of patients refuse Western medical treatments and use TCM alone. However, the survival impact of the latter is unknown. HYPOTHESES TESTED: Treatment with TCM alone is prognostically superior to PBC alone. Addition of PBC or TT or both TT to TCM improves survival. METHODS: In this prospective observational, non-interventional study of 1017 consecutive first-onset stage IV NSCLC patients with up to 10 years follow-up, 261 who Died of Disease (DOD) within 3 months were omitted, as they never got the optimal Western medical therapies. All 218 non-adenocarcinomas were also omitted, leaving 538 stage IV adenocarcinomas treated by TCM alone (n = 29), PBC alone (N = 19) and TCM and other Western medical combinations (299 TCM and PBC, 50 TCM and TT, 141 TCM and PBC and TT) with 3 - 120 months follow-up. Survivals were compared using Alive with Disease (AWD) and DOD as endpoints. RESULTS: The patients treated only with TCM had 7 months better median survival than those that received PBC alone (17 and 10 months). The patients that received TCM and PBC had a better median survival (24 months) than TCM alone and much better than PBC alone. None of the patients that received TCM alone survived > 54 months, whereas 18% of TCM and PBC patients survived much longer. Over the observation period of 3 - 120 months, survivals of TCM and TT, TCM and PBC and TT, and TCM and PBC were not different and therefore grouped as TCM and Western medicines. Median survival times of PBC alone and TCM alone were lower than that of TCM and Western medical treatments (p < 0.0001, 10, 17 and 27 months). CONCLUSIONS: Pulmonary stage IV adenocarcinoma patients with at least 3 months survival, treated with TCM alone have a significantly better survival than those treated with PBC alone. Adding Western PBC, TT or both to TCM further improves prognosis.

Avelumab First-Line Maintenance Therapy: Managing Patients With Advanced Urothelial Carcinoma.

BACKGROUND: The phase 3 of JAVELIN Bladder 100 trial demonstrated that avelumab first-line (1L) maintenance in addition to best supportive care significantly prolonged overall survival compared to best supportive care alone. It is now the standard of care for platinum-eligible patients with locally advanced or metastatic urothelial carcinoma that has not progressed with 1L platinum-containing chemotherapy. OBJECTIVES: This article provides considerations for oncology nurses to effectively implement avelumab 1L maintenance treatment in the clinical setting. METHODS: This article reviews clinical evidence and implications for oncology nurses caring for patients receiving avelumab 1L maintenance treatment. FINDINGS: Oncology nurses can provide comprehensive care for patients with advanced urothelial carcinoma and ensure the safe and appropriate use of avelumab 1L maintenance treatment by educating patients and caregivers, ensuring correct administration, and promptly recognizing and managing immune-related adverse events.

A sustainable hydrometallurgical strategy for recycling efficiently platinum from spent reforming petroleum catalyst.

Platinum (Pt) is one of the most precious metals with a variety of unique industrial applications, particularly in catalytic reactions, being its recovery, after use, essential. Therefore, this work proposes a simplified hydrometallurgical strategy to recover Pt efficiently from the original (no milling) spent petrochemical Pt catalyst using an economical and environmentally sustainable process. To that end, the effectiveness of a two-step workflow constituted by one microwave-assisted leaching step using a mixture of hydrochloric acid (HCl) and hydrogen peroxide (H2O2) followed by one ion-exchange purification step was developed and optimized. It was found that complete dissolution of Pt plus aluminum (Al) and iron (Fe) from the roasted original size catalyst was achieved after microwave-assisted leaching with 25% (v/v) HCl and 2% (v/v) H2O2 during 2 cycles of 60 s. Furthermore, a strong anionic exchange (Purogold™ A194) resin used for subsequent selective purification of Pt from Al and Fe was capable of effective separation of the metals: Pt in the eluate presented a purity of 98.1%, while Al, in the raffinate, presented a purity of 99.8%. In summation, it can be concluded that the overall process is a potentially good addition to a more circular economy as it manages to recover high-quality Pt for being reused as well as other by-products, whilst minimizing the consume of reagents, leaching time (and, thus, energy), and environmental impacts.

Avelumab as First-Line Maintenance Treatment in Locally Advanced or Metastatic Urothelial Carcinoma.

This work provides a summary of guideline recommendations and an expert position on the use of maintenance avelumab therapy based on a review of current international clinical practice guidelines for locally advanced or metastatic urothelial carcinoma (UC). A PubMed literature search was conducted in March 2022 (updated in July 2023) to identify guidelines for locally advanced or metastatic UC. An expert panel (four oncologists and one urologist) reviewed the guidelines and clinical evidence, and discussed practical questions regarding the use of avelumab maintenance therapy in this clinical setting. The National Comprehensive Cancer Network, European Association of Urology and European Society for Medical Oncology guidelines recommend first-line cisplatin-containing chemotherapy for cisplatin-eligible patients, carboplatin-gemcitabine for cisplatin-ineligible patients who are fit for carboplatin, or immunotherapy with programmed death ligand-1 (PD-L1) inhibitors (e.g. atezolizumab) in platinum-ineligible patients. Maintenance avelumab is recommended in patients with response/stable disease following chemotherapy (regardless of PD-L1 status). In patients who relapse after/during chemotherapy, options include immunotherapy, erdafitinib [in those with fibroblast growth factor receptor (FGFR) mutations], enfortumab vedotin or further chemotherapy. The expert panel provided the following practical guidance: (1) consider maintenance avelumab in all eligible patients; (2) continue avelumab until disease progression/unacceptable toxicity; (3) ideally, administer six cycles of platinum-based chemotherapy prior to maintenance avelumab; (4) perform radiological evaluation after four chemotherapy cycles and prior to maintenance avelumab; (5) carboplatin-gemcitabine followed by maintenance avelumab is preferred in cisplatin-ineligible patients (regardless of PD-L1 expression), but consider first-line immunotherapy in PD-L1-positive patients and platinum-ineligible patients (regardless of PD-L1 status); and (6) for patients who relapse on avelumab, second-line options include enfortumab vedotin, FGFR inhibitors (in those with FGFR mutations) or clinical trial inclusion. In conclusion, avelumab maintenance therapy is recommended following platinum-based chemotherapy in all eligible patients with locally advanced or metastatic UC, continued until disease progression or unacceptable toxicity.

A capacitive laser-induced graphene based aptasensor for SARS-CoV-2 detection in human saliva.

SARS-CoV-2 virus induced CoVID-19 pandemic has accelerated the development of diagnostic tools. Devices integrated with electrochemical biosensors may be an interesting alternative to respond to the high demand for testing, particularly in contexts where access to standard detection technologies is lacking. Aptamers as recognition elements are useful due to their stability, specificity, and sensitivity to binding target molecules. We have developed a non-invasive electrochemical aptamer-based biosensor targeting SARS-CoV-2 in human saliva. The aptamer is expected to detect the Spike protein of SARS-CoV-2 wildtype and its variants. Laser-induced graphene (LIG) electrodes coated with platinum nanoparticles were biofunctionalized with a biotin-tagged aptamer. Electrochemical Impedance Spectroscopy (EIS) for BA.1 sensing was conducted in sodium chloride/sodium bicarbonate solution supplemented with pooled saliva. To estimate sensing performance, the aptasensor was tested with contrived samples of UV-attenuated virions from 10 to 10,000 copies/ml. Selectivity was assessed by exposing the aptasensor to non-targeted viruses (hCoV-OC43, Influenza A, and RSV-A). EIS data outputs were further used to select a suitable response variable and cutoff frequency. Capacitance increases in response to the gradual loading of the attenuated BA.1. The aptasensor was sensitive and specific for BA.1 at a lower viral load (10-100 copies/ml) and was capable of discriminating between negative and positive contrived samples (with strain specificity against other viruses: OC43, Influenza A, and RSV-A). The aptasensor detected SARS-CoV-2 with an estimated LOD of 1790 copies/ml in contrived samples. In human clinical samples, the aptasensor presents an accuracy of 72%, with 75% of positive percent of agreement and 67% of negative percent of agreement. Our results show that the aptasensor is a promising candidate to detect SARS-CoV-2 during early stages of infection when virion concentrations are low, which may be useful for preventing the asymptomatic spread of CoVID-19.

Highly Activated Neuronal Firings Monitored by Implantable Microelectrode Array in the Paraventricular Thalamus of Insomnia Rats.

Insomnia is a common sleep disorder around the world, which is harmful to people's health, daily life, and work. The paraventricular thalamus (PVT) plays an essential role in the sleep-wake transition. However, high temporal-spatial resolution microdevice technology is lacking for accurate detection and regulation of deep brain nuclei. The means for analyzing sleep-wake mechanisms and treating sleep disorders are limited. To detect the relationship between the PVT and insomnia, we designed and fabricated a special microelectrode array (MEA) to record electrophysiological signals of the PVT for insomnia and control rats. Platinum nanoparticles (PtNPs) were modified onto an MEA, which caused the impedance to decrease and improved the signal-to-noise ratio. We established the model of insomnia in rats and analyzed and compared the neural signals in detail before and after insomnia. In insomnia, the spike firing rate was increased from 5.48 ± 0.28 spike/s to 7.39 ± 0.65 spike/s, and the power of local field potential (LFP) decreased in the delta frequency band and increased in the beta frequency band. Furthermore, the synchronicity between PVT neurons declined, and burst-like firing was observed. Our study found neurons of the PVT were more activated in the insomnia state than in the control state. It also provided an effective MEA to detect the deep brain signals at the cellular level, which conformed with macroscopical LFP and insomnia symptoms. These results laid the foundation for studying PVT and the sleep-wake mechanism and were also helpful for treating sleep disorders.

Chemodynamic/Photothermal Synergistic Cancer Immunotherapy Based on Yeast Microcapsule-Derived Au/Pt Nanoparticles.

In recent years, microbiota-based tumor immunotherapy has become a hotspot in cancer research. However, the use of microorganisms alone to activate the immune response for antitumor therapy was unsatisfactory. In this study, we biosynthesized gold nanoparticles (AuNPs) and platinum nanoparticles (PtNPs) based on yeast microcapsules to activate the immune response for antitumor treatment in synergy with chemodynamic therapy (CDT) and photothermal therapy (PTT). We generated AuNPs and PtNPs on yeast microcapsules (YAP) and fabricated nanoscale particles (Bre-YAP) by ultrasonic fragmentation and differential centrifugation. Bre-YAP retained the glucan component of yeast as an adjuvant; in the meantime, these two kinds of metal nanoparticles contained were excellent CDT and PTT mediators. By inspection, they could reach a high level of distribution in tumors and tumor-draining lymph nodes (TDLNs). Under the laser irradiation of tumors, this immunological nanomaterial significantly remodeled the microenvironments of tumors and TDLNs. The primary tumors were effectively inhibited or even eradicated, and the overall survival of mice was significantly improved as well. Therefore, yeast microcapsule-based Bre-YAP with immune properties could be used as an effective cancer treatment modality.

Antitumor potential of platinum(II) complexes of selenium donor ligands.

Platinum(II) coordination compounds are widely applied in clinics as anticancer drugs. In this review, we provide a summary of the reports on cytotoxic properties of platinum(II) complexes of selenium donor ligands along with a brief description of their structural features. It has been observed that the platinum(II) complexes of selenones and selenoethers display reasonable antitumor properties and in some cases their cytotoxic activity is greater than cisplatin. The complexes containing NH3 ligands along with selenones were found to exhibit better cytotoxicity compared to the binary Pt-selenone complexes. The mechanistic insights showed that these complexes exert antitumor activity through reactive oxygen species (ROS) generation and induction of apoptosis. The platinum-selenoether coordination compounds can self-assemble into spherical aggregates capable of self-delivery. The self-assembled Pt-selenium aggregates induce cell apoptosis via ROS, which leads to high selectivity between cancer cells and normal cells in cytotoxicity assays.

Pembrolizumab in combination with nab-paclitaxel for the treatment of patients with early-stage triple-negative breast cancer - A single-arm phase II trial (NeoImmunoboost, AGO-B-041).

BACKGROUND: Pembrolizumab is approved for the neoadjuvant/adjuvant treatment of early triple-negative breast cancer (TNBC) patients in combination with chemotherapy. The Keynote-522 trial used platinum chemotherapy. As neoadjuvant nab-paclitaxel (nP) is also highly effective in triple-negative breast cancer patients, this study investigates the response to nP-containing neoadjuvant chemotherapy in combination with pembrolizumab. PATIENTS AND METHODS: NeoImmunoboost (AGO-B-041/NCT03289819) is a multicenter, prospective single-arm phase II trial. Patients were treated with 12 weekly cycles of nP followed by four three-weekly cycles of epirubicin/cyclophosphamide. Pembrolizumab was given three-weekly in combination with these chemotherapies. The study was planned for 50 patients. After 25 patients, the study was amended to include a pre-chemotherapy single application of pembrolizumab. The primary aim was pathological complete response (pCR), and the secondary aims were safety and quality of life. RESULTS: Of 50 included patients, 33 (66.0%; 95%confidence interval: 51.2%-78.8%) had a (ypT0/is ypN0) pCR. The pCR rate in the per-protocol population (n = 39) was 71.8% (95%confidence interval: 55.1%-85.0%). The most common adverse events of any grade were fatigue (58.5%), peripheral sensory neuropathy (54.7%) and neutropenia (52.8%). The pCR rate in the cohort of 27 patients with a pre-chemotherapy pembrolizumab dose was 59.3%, and 73.9% in the 23 patients without pre-chemotherapy dose. CONCLUSIONS: pCR rates after NACT with nP and anthracycline combined with pembrolizumab are encouraging. With acceptable side-effect profiles, this treatment might be a reasonable alternative to platinum-containing chemotherapy in cases of contraindications. However, without data from randomised trials and long-term follow up, platinum/anthracycline/taxane-based chemotherapy remains the standard combination chemotherapy for pembrolizumab.

Chemotherapy response in low-grade serous ovarian carcinoma at a comprehensive cancer center: Readdressing the roles of platinum and cytotoxic therapies.

BACKGROUND: Data on platinum sensitivity of low-grade serous ovarian carcinoma (LGSOC) in the upfront setting is lacking, and there is limited and contradictory information on chemotherapy responses in recurrent disease. METHODS: Patients with LGSOC seen at a comprehensive cancer center from January 1, 1998 to September 30, 2021 were identified from institutional databases. Response to neoadjuvant chemotherapy (NACT) or adjuvant platinum-based chemotherapy and to second- to fifth-line regimens was retrospectively characterized by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Wilcoxon rank-sum and two-tailed Fisher exact tests were employed. RESULTS: Of 50 patients, 12 received platinum doublets for suboptimal residual disease and 11 as NACT. Of 12 patients with suboptimal residual disease, seven (58%) achieved objective responses (five partial responses [PRs] and two complete responses); of the 11 patients who underwent NACT, one (9%) achieved a PR (p = .027). The 15 remaining patients had stable disease on first-line platinum chemotherapy. Of 44 patients who recurred, 20 had RECIST-evaluable responses to second-line and 27 to third-line chemotherapy. Objective response rates to platinum-based chemotherapy were 22% (two of nine) in the second line and 10% (one of 10) in the third. In second and third lines, highest response rates were observed with nonplatinum chemotherapy with bevacizumab, at 100% (two of two) and 30% (three of 10), respectively. CONCLUSIONS: Primary platinum-based chemotherapy has moderate activity in LGSOC and minimal activity in the recurrent setting, suggesting standard definitions of platinum sensitivity may not apply in LGSOC. In the second and third lines, nonplatinum chemotherapy/bevacizumab elicited the highest response rates.

Platin-C containing nanoparticles: a recipe for the delivery of curcumin-cisplatin combination chemotherapeutics to mitochondria.

The success story of cisplatin spans over six decades now and yet it continues to be the key player in most chemotherapeutic regimens. Numerous efforts have been made to improve its efficacy, address its shortcomings, and overcome drug resistance. One such strategy is to develop new platinum(IV)-based prodrugs with functionally active ligands to deliver combination therapeutics. This strategy not only enables the drug candidate to access multiple drug targets but also enhances the kinetic inertness of platinum complexes and thereby ensures greater accumulation of active drugs at the target site. We report the synthesis of Platin-C, a platinum(IV)-based cisplatin prodrug tethered to the active component of ancient herbal medicine, curcumin, as one of the axial ligands. This combination complex showed improved chemotherapeutic efficacy in cisplatin resistant A2780/CP70 cell lines compared with the individual components. An amine-terminated biodegradable polymer was suitably functionalized with the triphenylphosphonium (TPP) cation to obtain a mitochondria-directed drug delivery platform. Quantification of Platin-C loading into these NPs using complementary techniques employing curcumin optical properties in high-performance liquid chromatography and platinum-based inductively coupled plasma mass spectrometry evidenced efficacious payload incorporation resulting in functional activities of both the components. Stability studies for a period of one week indicated that the NPs remain stable, enabling substantial loading and controlled release of the prodrug. The targeting nanoparticle (NP) platform was utilized to deliver Platin-C primarily in the mitochondrial network of cancer cells as monitored using confocal microscopy employing the green fluorescence of the curcumin pendant. Our studies showed that amine terminated NPs were relatively less efficient in their ability to target mitochondria despite being positively charged. This re-validated the importance of lipophilic positively charged TPP surface functionalities to successfully target cellular mitochondria. We validated the capabilities of Platin-C and its mitochondria-targeting nanoparticles towards inflicting mitochondria-directed activity in cisplatin-sensitive and cisplatin-resistant cell lines. Furthermore, our studies also demonstrated the effectiveness of Platin-C incorporated targeting NPs in attenuating cellular inflammatory markers by utilizing the curcumin component. This study advances our understanding of the cisplatin prodrug approach to combine chemotherapeutic and inflammatory effects in accessing combinatory pathways.