A versatile nanoplatform carrying cascade Pt nanozymes remodeling tumor microenvironment for amplified sonodynamic/chemo therapy of thyroid cancer.

Thyroid cancer is increasing globally, with anaplastic thyroid carcinoma (ATC) being the most aggressive type and having a poor prognosis. Current clinical treatments for thyroid cancer present numerous challenges, including invasiveness and the necessity of lifelong medication. Furthermore, a significant portion of patients with ATC experience cancer recurrence and metastasis. To overcome this dilemma, we developed a pH-responsive biomimetic nanocarrier (CLP@HP-A) through the incorporation of Chlorin e6 (Ce6) and Lenvatinib (Len) within hollow polydopamine nanoparticles (HP) that were further modified with platinum nanoparticles (Pt), enabling synergistic chemotherapy and sonodynamic therapy. The CLP@HP-A nanocarriers exhibited specific binding with galectin-3 receptors, facilitating their internalization through receptor-mediated endocytosis for targeted drug delivery. Upon exposure to ultrasound (US) irradiation, Ce6 rapidly generated reactive oxygen species (ROS) to induce significant oxidative stress and trigger apoptosis in tumor cells. Additionally, Pt not only alleviated tumor hypoxia by catalyzing the conversion of H2O2 to oxygen (O2) but also augmented intracellular ROS levels through the production of hydroxyl radicals (•OH), thereby enhancing the efficacy of sonodynamic therapy. Moreover, Len demonstrated a potent cytotoxic effect on thyroid cancer cells through the induction of apoptosis. Transcriptomics analysis findings additionally corroborated that CLP@HP-A effectively triggered cancer cell apoptosis, thereby serving as a crucial mechanism for its cytotoxic effects. In conclusion, the integration of sonodynamic/chemo combination therapy with targeted drug delivery systems offers a novel approach to the management of malignant tumors.

Efficient chlorination reaction of Pt/RuO2/g-C3N4 under visible light irradiation for simultaneous removal of ammonia and bacteria from mariculture wastewater.

The removal of ammonia nitrogen (NH4+-N) and bacteria from aquaculture wastewater holds paramount ecological and production significance. In this study, Pt/RuO2/g-C3N4 photocatalysts were prepared by depositing Pt and RuO2 particles onto g-C3N4. The physicochemical properties of photocatalysts were explored by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), X-ray diffraction (XRD), and UV-vis diffuse reflectance spectrometer (UV-vis DRS). The photocatalysts were then applied to the removal of both NH4+-N and bacteria from simulated mariculture wastewater. The results clarified that the removals of both NH4+-N and bacteria were in the sequence of g-C3N4 < RuO2/g-C3N4 < Pt/g-C3N4 < Pt/RuO2/g-C3N4. This magnificent photocatalytic ability of Pt/RuO2/g-C3N4 can be interpreted by the transfer of holes from g-C3N4 to RuO2 to facilitate the in situ generation of HClO from Cl- in wastewater, while Pt extracts photogenerated electrons for H2 formation to enhance the reaction. The removal of NH4+-N and disinfection effect were more pronounced in simulated seawater than in pure water. The removal efficiency of NH4+-N increases with an increase in pH of wastewater, while the bactericidal effect was more significant under a lower pH in a pH range of 6-9. In actual seawater aquaculture wastewater, Pt/RuO2/g-C3N4 still exhibits effective removal efficiency of NH4+-N and bactericidal performance under sunlight. This study provides an alternative avenue for removement of NH4+-N and bacteria from saline waters under sunlight.

Spatial confinement: An effective strategy to improve H2O and SO2 resistance of the expandable graphite-modified TiO2-supported Pt nanocatalysts for CO oxidation.

The expandable graphite (EG) modified TiO2 nanocomposites were prepared by the high shear method using the TiO2 nanoparticles (NPs) and EG as precursors, in which the amount of EG doped in TiO2 was 10 wt.%. Followed by the impregnation method, adjusting the pH of the solution to 10, and using the electrostatic adsorption to achieve spatial confinement, the Pt elements were mainly distributed on the exposed TiO2, thus generating the Pt/10EG-TiO2-10 catalyst. The best CO oxidation activity with the excellent resistance to H2O and SO2 was obtained over the Pt/10EG-TiO2-10 catalyst: CO conversion after 36 hr of the reaction was ca. 85% under the harsh condition of 10 vol.% H2O and 100 ppm SO2 at a high gaseous hourly space velocity (GHSV) of 400,000 hr-1. Physicochemical properties of the catalysts were characterized by various techniques. The results showed that the electrostatic adsorption, which riveted the Pt elements mainly on the exposed TiO2 of the support surface, reduced the dispersion of Pt NPs on EG and achieved the effective dispersion of Pt NPs, hence significantly improving CO oxidation activity over the Pt/10EG-TiO2-10 catalyst. The 10 wt.% EG doped in TiO2 caused the TiO2 support to form a more hydrophobic surface, which reduced the adsorption of H2O and SO2 on the catalyst, greatly inhibited deposition of the TiOSO4 and formation of the PtSO4 species as well as suppressed the oxidation of SO2, thus resulting in an improvement in the resistance to H2O and SO2 of the Pt/10EG-TiO2-10 catalyst.

Quantifying Intracellular Platinum Accumulation Using Inductively Coupled Mass Spectrometry.

The platinum-based anticancer drug cisplatin and its analog carboplatin are the most used chemotherapeutic agents worldwide. It is estimated that approximately half of all cancer patients are treated with platinum drugs at some point during the therapy regimen. Cisplatin covalently binds to purine nucleobases to form DNA adducts. Cisplatin therapy is faced with two key challenges. First, despite the initial response, many patients develop cisplatin resistance. Reduced cellular accumulation of cisplatin is one common cause of therapy resistance. Second, cisplatin treatment causes general cytotoxicity, leading to severe side effects. Monitoring the subcellular concentration of platinum chemotherapeutics will help yield clinical efficacy with the minimum possible dose. Inductively coupled plasma-mass spectrometry (ICP-MS) is an analytical technique to quantify the elemental composition of various types of liquified bulk samples with high sensitivity. This article describes quantifying cisplatin accumulation in chromatin and total cell lysate using ICP-MS. The method involves treating cells with cisplatin, isolating RNA-free DNA, digesting samples, ICP-MS instrumentation, and data analysis. Although we describe these steps in one cancer cell line, the protocol can be adapted to any cell line or tissue. The protocol should be a valuable resource for investigators interested in accurate measurement of subcellular concentration of platinum and other metallo-drugs. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Cell culture conditions for A2780 cells and cisplatin treatment Basic Protocol 2: Isolating cellular fractions and sample quantitation Basic Protocol 3: Sample digestion, ICP-MS data collection, and analysis.

A nomogram to predict platinum-sensitivity and survival outcome in women with advanced epithelial ovarian cancer.

OBJECTIVE: This study presents the development and validation of a nomogram aimed at predicting platinum-sensitivity and survival outcomes in women with advanced epithelial ovarian cancer (EOC). MATERIALS AND METHODS: Data from a retrospective cohort of women diagnosed with stage III/IV EOC between Jan 2011 and Dec 2021 treated at our institute were collected. Clinical and pathological characteristics were analyzed using logistic regression analysis to identify independent predictors of platinum-sensitivity. Impact on progression-free (PFS) and overall survival (OS) was determined by Kaplan-Meier and Cox regression analysis. A nomogram was constructed based on the significant predictors, and its performance was evaluated using calibration, discrimination, and validation analyses. RESULTS: Of the 210 patients, 139 (66.19%) had platinum-sensitive and 71 (33.81%) were platinum-resistant disease. On multivariate analysis, platinum-resistance correlated with neoadjuvant chemotherapy (OR 2.15; 95% CI 1.10-4.21), clear cell/mucinous histology (OR 5.04; 95% CI 2.20-11.54), and sub-optimal debulking status (OR 3.37; 95% CI 1.44-7.91). Median PFS and OS were also significantly shorter for patients with neoadjuvant chemotherapy (23 vs. 10 months and 69 vs. 29 months, respectively), clear cell/mucinous histology (15 vs. 3 months and 63 vs. 11 months, respectively), and suboptimal debulking (26 vs. 5 months and 78 vs. 24 months, respectively). The nomogram demonstrated good predictive accuracy for platinum-sensitivity in the cohort as indicated by high concordance index of 0.745. Calibration plots showed excellent agreement and internal validation further confirmed the reliability of the nomogram's performance. CONCLUSION: A novel predictive nomogram based on type of initial treatment, histology, and debulking status was developed, which provides a friendly and reliable tool for predicting platinum-sensitivity and survival outcomes in women with advanced EOC. Its application may assist clinicians in individualizing treatment decisions.

Nanostructured mesoporous silica carriers for platinum-based conjugates with anti-inflammatory agents.

This review discusses the relationship between inflammation and cancer initiation and progression, which has prompted research into anti-inflammatory approaches for cancer prevention and treatment. Specifically, it focuses on the use of inflammation-reducing agents to enhance the effectiveness of tumor treatment methods. These agents are combined with platinum(II)-based antitumor drugs to create multifunctional platinum(IV) prodrugs, allowing for simultaneous delivery to tumor cells in a specific ratio. Once inside the cells and subjected to intracellular reduction, both components can act in parallel through distinct pathways. Motivated by the objective of reducing the systemic toxicity associated with contemporary chemotherapy, and with the aim of leveraging the passive enhanced permeability and retention effect exhibited by nanostructured materials to improve their accumulation within tumor tissues, the platinum(IV) complexes have been efficiently loaded into mesoporous silica SBA-15 material. The resulting nanostructured materials are capable of providing controlled release of the conjugates when subjected to simulated plasma conditions. This feature suggests the potential for extended circulation within the body in vivo, with minimal premature release of the drug before reaching the intended target site. The primary emphasis of this review is on research that integrates these two approaches to develop chemotherapeutic treatments that are both more efficient and less harmful.

Platinum-perovskite nanocomposite-based Exosensor for specific detection of prostate cancer in clinical settings.

Exosomes, extracellular vesicles (EVs) with an average size of 50-150 nm, transfer various biomolecules and exchange signaling molecules between cells in a paracrine manner. Molecular investigations have revealed that EVs can reflect real-time metabolic changes in normal- and cancer-origin cells and thus harbor valid diagnostic biomarkers. Despite these advantages, the detection of low concentrations of cancer cell EVs in biological fluids is still a great challenge. Here, a new electrochemical Exosensor based on platinum-perovskite is developed for the direct detection of EVs using a biotinylated monoclonal CD63 antibody as a capture element. The label-free method exhibited higher sensitivity with a lower limit of quantification of 2000 EVs/µL with a dynamic linear range (LDR) of 2000 to 14,000 EVs/µL compared with other available methods. To enhance the selectivity of detection, EVs were simultaneously sandwiched between secondary antibodies of PSA (prostate-specific antigen), as an FDA-approved prostate cancer biomarker. Data indicated that this Exosensor can distinguish normal and cancer EVs in samples from healthy individuals and prostate cancer patients. Taken together, this technology offers a unique approach to label-free quantification of EVs and cancer detection in the early stages.

Engineering Novel Amphiphilic Platinum(IV) Complexes to Co-Deliver Cisplatin and Doxorubicin.

In this study, we report a novel platinum-doxorubicin conjugate that demonstrates superior therapeutic indices to cisplatin, doxorubicin, or their combination, which are commonly used in cancer treatment. This new molecular structure (1) was formed by conjugating an amphiphilic Pt(IV) prodrug of cisplatin with doxorubicin. Due to its amphiphilic nature, the Pt(IV)-doxorubicin conjugate effectively penetrates cell membranes, delivering both cisplatin and doxorubicin payloads intracellularly. The intracellular accumulation of these payloads was assessed using graphite furnace atomic absorption spectrometry and fluorescence imaging. Since the therapeutic effects of cisplatin and doxorubicin stem from their ability to target nuclear DNA, we hypothesized that the amphiphilic Pt(IV)-doxorubicin conjugate (1) would effectively induce nuclear DNA damage toward killing cancer cells. To test this hypothesis, we used flow the cytometric analysis of phosphorylated H2AX (γH2AX), a biomarker of nuclear DNA damage. The Pt(IV)-doxorubicin conjugate (1) markedly induced γH2AX in treated MDA-MB-231 breast cancer cells, showing higher levels than cells treated with either cisplatin or doxorubicin alone. Furthermore, MTT cell viability assays revealed that the enhanced DNA-damaging capability of complex 1 resulted in superior cytotoxicity and selectivity against human cancer cells compared to cisplatin, doxorubicin, or their combination. Overall, the development of this amphiphilic Pt(IV)-doxorubicin conjugate represents a new form of combination therapy with improved therapeutic efficacy.

Core-satellite-structured magnetic nanozyme enables the ultrasensitive colorimetric detection of multiple drug residues on lateral flow immunoassay.

BACKGROUND: Excessive use of veterinary drugs causes severely environmental pollution and agricultural pollution, and poses great threat to human health. A simple method for the rapid, highly sensitive, and on-site monitoring of veterinary drug residues in complex samples remains lacking. RESULTS: In this study, we propose a catalytically enhanced colorimetric lateral flow immunoassay (LFA) based on a novel core-satellite-structured magnetic nanozyme (Fe-Au@Pt) that can simultaneously and quantitatively detect three common veterinary drugs, namely, gentamicin (GM), streptomycin (STR), and clenbuterol (CLE), within a short testing time (<30 min). The Fe-Au@Pt nanozyme was simply prepared through the self-assembly of numerous Au@Pt nanoparticles on a large Fe3O4 core via electrostatic adhesion, which exhibited the advantages of high peroxidase-like activity, strong magnetic responsiveness, and multiple catalytic sites. Under the dual-signal amplification effect of magnetic enrichment and catalytic enhancement, the proposed nanozyme-LFA allowed the multiplex detection of STR, CLE, and GM with detection limits of 10.1, 6.3, and 1.1 pg/mL, respectively. SIGNIFICANCE: The developed Fe-Au@Pt-LFA achieves direct, simultaneous, and accurate detection of three target drugs in food samples (honey, milk, and pork). The proposed assay shows great potential for application in the real-time monitoring of small-molecule pollutants in complex environment.

3D Film-Like Nanozyme with a Synergistic Amplification Effect for the Ultrasensitive Immunochromatographic Detection of Respiratory Viruses.

Greatly improving the sensitivity and detection range of lateral flow immunoassays (LFAs) by at least 100 times without using additional instruments remains challenging. Herein, we develop a three-dimensional (3D) film-like nanozyme (GO-Pt30-AuPt5) by ordered assembly of one layer of 30 nm Pt nanoparticles (NPs) and one layer of small Au@Pt satellites (5 nm) onto a two-dimensional (2D) graphene oxide (GO) nanofilm, in which GO greatly increased the interface area and stability of the nanozyme whereas Pt and Au@Pt NPs synergistically enhanced colorimetric/catalytic activities. The grafting of outer Au@Pt satellites converted the 2D nanofilm into a 3D flexible nanozyme with numerous catalytic sites for enzymatic deposition signal amplification and binding sites for target capture. The introduction of GO-Pt30-AuPt5 into multiplex LFA achieved the ultrasensitive and simultaneous detection of two important respiratory viruses with sensitivity of 1 pg/mL level, which was about 100 times higher than that without signal enrichment and at least 20 and 1900 times higher than those of traditional enzyme-linked immunosorbent assay and AuNP-based LFA, respectively. The clinical utility of the proposed assay was validated through the diagnosis of 49 real clinical respiratory tract specimens. Our proposed LFA shows great potential for the ultrasensitive screening of pathogens in the field.

Biotin-Pt(IV)-Ru(II)-Boron-Dipyrromethene Prodrug as "Platin Bullet" for Targeted Chemo- and Photodynamic Therapy.

Using the principle of "Magic Bullet", a cisplatin-derived platinum(IV) prodrug heterobimetallic Pt(IV)-Ru(II) complex, cis,cis,trans-[Pt(NH3)2Cl2{Ru(tpy-BODIPY)(tpy-COO)}(biotin)]Cl2 (Pt-Ru-B, 2), having two axial ligands, namely, biotin as water-soluble B-vitamin for enhanced cellular uptake and a BODIPY-ruthenium(II) (Ru-B, 1) photosensitizer having N,N,N-donor tpy (4'-phenyl-2,2':6',2″-terpyridine) bonded to boron-dipyrromethene (BODIPY), is developed as a "Platin Bullet" for targeted photodynamic therapy (PDT). Pt-Ru-B exhibited intense absorption near 500 nm and emission near 513 nm (λex = 488 nm) in a 10% dimethyl sulfoxide-Dulbecco's phosphate-buffered saline medium (pH 7.2). The BODIPY complex on light activation generates singlet oxygen as the reactive oxygen species (ROS) giving a quantum yield (ΦΔ) of ∼0.64 from 1,3-diphenylisobenzofuran experiments. Pt-Ru-B exhibited preferential cellular uptake in cancer cells over noncancerous cells. The dichlorodihydrofluorescein diacetate assay confirmed the generation of cellular ROS. Confocal images revealed its mitochondrial internalization. Pt-Ru-B showed submicromolar photocytotoxicity in visible light (400-700 nm) in A549 and multidrug-resistant MDA-MB-231 cancer cells. It remained nontoxic in the dark and less toxic in nontumorigenic cells. Cellular apoptosis and alteration of the mitochondrial membrane potential were evidenced from the respective Annexin V-FITC/propidium iodide assay and JC-1 dye assay. A wound healing assay using A549 cells and Pt-Ru-B revealed inhibition of cancer cell migration, highlighting its potential as an antimetastatic agent.

Nanozyme Decorated Metal-Organic Framework Nanosheet for Enhanced Photodynamic Therapy Against Hypoxic Tumor.

Introduction: Photodynamic therapy (PDT) has attracted increasing attention in the clinical treatment of epidermal and luminal tumors. However, the PDT efficacy in practice is severely impeded by tumor hypoxia and the adverse factors associated with hydrophobic photosensitizers (PSs), including low delivery capacity, poor photoactivity and limited ROS diffusion. In this study, Pt nanozymes decorated two-dimensional (2D) porphyrin metal-organic framework (MOF) nanosheets (PMOF@HA) were fabricated and investigated to conquer the obstacles of PDT against hypoxic tumors. Materials and Methods: PMOF@HA was synthesized by the coordination of transition metal iron (Zr4+) and PS (TCPP), in situ generation of Pt nanozyme and surface modification with hyaluronic acid (HA). The abilities of hypoxic relief and ROS generation were evaluated by detecting the changes of O2 and 1O2 concentration. The cellular uptake was investigated using flow cytometry and confocal laser scanning microscopy. The SMMC-7721 cells and the subcutaneous tumor-bearing mice were used to demonstrate the PDT efficacy of PMOF@HA in vitro and in vivo, respectively. Results: Benefiting from the 2D structure and inherent properties of MOF materials, the prepared PMOF@HA could not only serve as nano-PS with high PS loading but also ensure the rational distance between PS molecules to avoid aggregation-induced quenching, enhance the photosensitive activity and promote the rapid diffusion of generated radical oxide species (ROS). Meanwhile, Pt nanozymes with catalase-like activity effectively catalyzed intratumoral overproduced H2O2 into O2 to alleviate tumor hypoxia. Additionally, PMOF@HA, with the help of externally coated HA, significantly improved the stability and increased the cell uptake by CD44 overexpressed tumor cells to strengthen O2 self-supply and PDT efficacy. Conclusion: This study provided a new strategy of integrating 2D porphyrin MOF nanosheets with nanozymes to conquer the obstacles of PDT against hypoxic tumors.

Cu-MOFs@AuPtNPs nanozyme-based immunosorbent assay for colorimetric detection of alpha-fetoprotein.

Accurate detection of tumor biomarkers in blood is crucial for diagnosing and treating tumor disease. In this study, a metal enzyme-linked immunosorbent assay (MeLISA) was fabricated for the ultrasensitive and naked-eye detection of tumor biomarker alpha-fetoprotein (AFP) in clinical serum samples. Herein, novel copper metal-organic frameworks and gold platinum nanoparticle composites (Cu-MOFs@AuPtNPs) were synthesized for the first time by an in situ method, which showed an enormous specific surface area and excellent peroxidase (POx) mimicking properties. Cu-MOFs@AuPtNPs linked with antibodies targeting AFP served as a signal nanoprobe to amplify the detection signal. Additionally, the specificity of MeLISA was significantly enhanced through a conventional antigen-antibody reaction and efficient blocking of non-specific sites with BSA. Under optimal conditions, the sandwich-type MeLISA exhibited a wide range from 0.001 to 1000 ng mL-1 (R2 = 0.997) and a low detection limit of 0.86 pg mL-1 (S/N = 3) with acceptable stability, selectivity, and reproducibility. It is noteworthy that the suggested MeLISA performed exceptionally well in detecting clinical serum samples, which were visible to the naked eye and did not require complex platforms. To sum up, the innovative MeLISA based on Cu-MOFs@AuPtNPs provides an alternative method for early cancer diagnosis, particularly in economically backward areas where simple diagnostic apparatus is extremely desirable.

Multicomponent Gas Sensing Fiber Probe System Based on Platinum Coated Capillary Enhanced Raman Spectroscopy.

This paper proposes a novel multicomponent gas-sensing optical fiber probe system. It utilizes a precisely engineered Platinum-coated capillary fabricated via Atomic Layer Deposition (ALD) technology as the core for enhanced Raman spectroscopy, marking the first application of ALD in creating such a structure for gas Raman sensing. The noble metal capillary gas Raman probe demonstrates a low detection limit of 55 ppm for CO2 with a 30 s exposure time and good repeatability in multicomponent gas sensing. The capillary exhibits excellent stability, environmental resistance, and a large core diameter, enabling a rapid gas exchange rate and making it suitable for practical applications.

Promising antibiofilm formation: Liquid phase pulsed laser ablation synthesis of Graphene Oxide@Platinum core-shell nanoparticles.

The increasing prevalence of multi-drug resistance in pathogenic bacteria has rendered antibiotics ineffective, necessitating the exploration of alternative antibacterial approaches. Consequently, research efforts have shifted towards developing new antibiotics and improving the efficacy of existing ones. In the present study, novel core shell graphene oxide@platinum nanoparticles (GRO@Pt-NPs) and their unchanging form have been synthesized using the two-step pulsed laser ablation in liquid (PLAL) technique. The first step involved using the graphene target to create graphene nanoparticles (GRO-NPs), followed by the ablation of GRO-NPs inside platinum nanoparticles (Pt-NPs). To characterize the nanoparticles, various methods were employed, including UV-VIS, transmission electron microscopy (TEM), energy dispersive X-ray (EDX), mapping tests, and X-ray diffraction (XRD). The anti-bacterial and anti-biofilm properties of the nanoparticles were investigated. TEM data confirm the creation of GRO@Pt-NPs. The average particle size was 11 nm for GRO-NPs, 14 nm for Pt-NPs, and 26 nm for GRO@Pt-NPs. The results demonstrate that the created GRO@Pt-NPs have strong antibacterial properties. This pattern is mostly produced through the accumulation of GRO@Pt-NPs on the bacterial surface of Klebsiella pneumoniae (K. pneumoniae) and Enterococcus faecium (E. faecium). The inhibition zones against K. pneumoniae and E. faecium when GRO-NPs were used alone were found to be 11.80 mm and 11.50 mm, respectively. For Pt-NPs, the inhibition zones of E. faecium and K. pneumoniae were 20.50 mm and 16.50 mm, respectively. The utilization of GRO@Pt-NPs resulted in a significant increase in these values, with inhibitory rates of 25.50 mm for E. faecium and 20.45 mm for K. pneumoniae. The antibacterial results were more potent in the core-shell structure than the GRO-NPs alone or Pt-NPs alone. The current work uses, for the first time, a fast and effective technique to synthesize the GRO@Pt-NPs by PLAL method, and the preparation has high clinical potential for prospective use as an antibacterial agent.

Assessing anticancer properties of PEGylated platinum nanoparticles on human breast cancer cell lines usingin-vitroassays.

This study describes the in-vitro cytotoxic effects of PEG-400 (Polyethylene glycol-400)-capped platinum nanoparticles (PEGylated Pt NPs) on both normal and cancer cell lines. Structural characterization was carried out using x-ray diffraction and Raman spectroscopy with an average crystallite size 5.7 nm, and morphological assessment using Scanning electron microscopy (SEM) revealed the presence of spherical platinum nanoparticles. The results of energy-dispersive x-ray spectroscopy (EDX) showed a higher percentage fraction of platinum content by weight, along with carbon and oxygen, which are expected from the capping agent, confirming the purity of the platinum sample. The dynamic light scattering experiment revealed an average hydrodynamic diameter of 353.6 nm for the PEGylated Pt NPs. The cytotoxicity profile of PEGylated Pt NPs was assessed on a normal cell line (L929) and a breast cancer cell line (MCF-7) using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The results revealed an IC50of 79.18 µg ml-1on the cancer cell line and non-toxic behaviour on the normal cell line. In the dual staining apoptosis assay, it was observed that the mortality of cells cultured in conjunction with platinum nanoparticles intensified and the proliferative activity of MCF-7 cells gradually diminished over time in correlation with the increasing concentration of the PEGylated Pt NPs sample. Thein vitroDCFH-DA assay for oxidative stress assessment in nanoparticle-treated cells unveiled the mechanistic background of the anticancer activity of PEGylated platinum nanoparticles as ROS-assisted mitochondrial dysfunction.

Early Circulating Tumor DNA Shedding Kinetics for Prediction of Platinum Sensitivity in Patients With Small Cell Lung Cancer.

PURPOSE: Small cell lung cancer (SCLC) is characterized by rapid progression after platinum resistance. Circulating tumor (ctDNA) dynamics early in treatment may help determine platinum sensitivity. MATERIALS AND METHODS: Serial plasma samples were collected from patients receiving platinum-based chemotherapy for SCLC on the first 3 days of cycle one and on the first days of subsequent cycles with paired samples collected both before and again after infusions. Tumor-informed plasma analysis was carried out using CAncer Personalized Profiling by deep Sequencing (CAPP-Seq). The mean variant allele frequency (VAF) of all pretreatment mutations was tracked in subsequent blood draws and correlated with radiologic response. RESULTS: ctDNA kinetics were assessed in 122 samples from 21 patients. Pretreatment VAF did not differ significantly between patients who did and did not respond to chemotherapy (mean 22.5% v 4.6%, P = .17). A slight increase in ctDNA on cycle 1, day 1 immediately post-treatment was seen in six of the seven patients with available draws (fold change from baseline: 1.01-1.44), half of whom achieved a response. All patients who responded had a >2-fold decrease in mean VAF on cycle 2 day 1 (C2D1). Progression-free survival (PFS) and overall survival (OS) were significantly longer in patients with a >2-fold decrease in mean VAF after one treatment cycle (6.8 v 2.6 months, log-rank P = .0004 and 21.7 v 6.4 months, log rank P = .04, respectively). CONCLUSION: A >2-fold decrease in ctDNA concentration was observed by C2D1 in all patients who were sensitive to platinum-based therapy and was associated with longer PFS and OS.

Transferrin-Modified Carprofen Platinum(IV) Nanoparticles as Antimetastasis Agents with Tumor Targeting, Inflammation Inhibition, Epithelial-Mesenchymal Transition Suppression, and Immune Activation Properties.

The inflammatory microenvironment is a central driver of tumor metastasis, intimately associated with the promotion of epithelial-mesenchymal transition (EMT) and immune suppression. Here, transferrin-modified carprofen platinum(IV) nanoparticles Tf-NPs@CPF2-Pt(IV) with promising antiproliferative and antimetastatic properties were developed, which activated by inhibiting inflammation, suppressing EMT, and activating immune responses besides causing DNA injury. The nanoparticles released the active ingredient CPF2-Pt(IV) in a sustained manner and offered enhanced pharmacokinetic properties compared to free CPF2-Pt(IV) in vivo. Additionally, they possessed satisfactory tumor targeting effects via the transferrin motif. Serious DNA damage was induced with the upregulation of γ-H2AX and P53, and the mitochondria-mediated apoptotic pathway Bcl-2/Bax/caspase3 was initiated. Inflammation was alleviated by inhibiting COX-2 and MMP9 and decreasing inflammatory cytokines TNF-α and IL-6. Subsequently, the EMT was reversed by inhibiting the Wnt/ß-catenin pathway. Furthermore, the antitumor immunity was provoked by blocking the immune checkpoint PD-L1 and increasing CD3+ and CD8+ T lymphocytes in tumors.

Synthesis, Photo-Characterizations, and Pre-Clinical Studies on Advanced Cellular and Animal Models of Zinc(II) and Platinum(II) Sulfonyl-Substituted Phthalocyanines for Enhanced Vascular-Targeted Photodynamic Therapy.

Two phthalocyanine derivatives tetra-peripherally substituted with tert-butylsulfonyl groups and coordinating either zinc(II) or platinum(II) ions have been synthesized and subsequently investigated in terms of their optical and photochemical properties, as well as biological activity in cellular, tissue-engineered, and animal models. Our research has revealed that both synthesized phthalocyanines are effective generators of reactive oxygen species (ROS). PtSO2tBu demonstrated an outstanding ability to generate singlet oxygen (ΦΔ = 0.87-0.99), while ZnSO2tBu in addition to 1O2 (ΦΔ = 0.45-0.48) generated efficiently other ROS, in particular ·OH. Considering future biomedical applications, the affinity of the tested phthalocyanines for biological membranes (partition coefficient; log Pow) and their primary interaction with serum albumin were also determined. To facilitate their biological administration, a water-dispersible formulation of these phthalocyanines was developed using Pluronic triblock copolymers to prevent self-aggregation and improve their delivery to cancer cells and tissues. The results showed a significant increase in cellular uptake and phototoxicity when phthalocyanines were incorporated into the customizable polymeric micelles. Moreover, the improved distribution in the body and photodynamic efficacy of the encapsulated phthalocyanines were investigated in hiPSC-delivered organoids and BALB/c mice bearing CT26 tumors. Both photosensitizers exhibit strong antitumor activity. Notably, vascular-targeted photodynamic therapy (V-PDT) led to complete tumor eradication in 84% of ZnSO2tBu and 100% of PtSO2tBu-treated mice, and no recurrence has so far been observed for up to five months after treatment. In the case of PtSO2tBu, the effect was significantly stronger, offering a wider range of light doses suitable for achieving effective PDT.

Amorphous PtOx-engineered Pt@WO3 nanozymes with efficient NAD+ generation for an electrochemical cascade biosensor.

Bioactive NAD+ mediated multiple biocatalytic pathways in metabolic networks. Refining the structure of NADH oxidase-like (NOX) mimics to efficiently replenish NAD+ has been promising but challenging in NAD+-dependent dehydrogenase electrochemical cascade biosensing. Herein, we discovered that PtOx structures, formed via lattice oxygen translocation from WO3 to Pt NPs at the interface, potentially activate and modulate the NOX-like functionality in Pt@WO3 nanosheets. Incorporating PtOx leads to a more positive valence of Pt species within Pt/PtOx@WO3-x, where the PtO2 species serve as preeminent reaction sites for NADH coordination, activation, and dehydrogenation. Consequently, such nanozymes display enhanced NOX-like activity towards NADH oxidation in comparison to Pt@WO3. Ultimately, the 650-Pt/PtOx@WO3-x nanozyme is employed in an electrochemical cascade biosensor for ß-hydroxybutyrate (HB) detection, achieving a calculated detection limit of 25 µM. This study offers insights into PtOx activation in Pt-based NOX mimics and supports the future development of NAD+/NADH-dependent electrochemical biosensors.