Cancer T24 Cells Research Articles

A mitochondria-interfering nanocomplex cooperates with photodynamic therapy to boost antitumor immunity.

Immunotherapeutics against triple-negative breast cancer (TNBC) hold great promise. In this work, we provide a combination therapy for simultaneous increasing tumor immunogenicity and down-regulating programmed cell death ligand 1 (PD-L1) to boost antitumor immunity in TNBC. We prepare bis (diethyldithiocarbamate)-copper/indocyanine green nanoparticles (CuET/ICG NPs) simply in aqueous with one-pot method. CuET/ICG NPs interfere mitochondria, reduce oxygen consumption, and alleviate tumor hypoxia to potentiate photodynamic therapy (PDT) for amplifying immunogenic cell death (ICD). Meanwhile, mitochondria dysfunction leads to energy stress and activates AMPK pathway. As a result, CuET/ICG NPs downregulates membrane PD-L1 (mPD-L1) on both 4T1 cancer cells and cancer stem cells (CSCs) through AMP-activated protein kinase (AMPK)-mediated pathway in hypoxia. Cooperatively, the combinational therapy activates antitumor immunity and triggers long lasting immune memory response to resist tumor re-challenge. Our study represents an attempt that conquers tumor immunosuppressive microenvironment with simple biomedical materials and multimodality treatments.

Copper-cobalt peroxide nanoparticles: a biomimetic cascade reaction for enhanced Fenton-like therapy at physiologically relevant pH.

Traditional Fenton-like reactions, commonly employed in chemodynamic therapy (CDT) for cancer treatment, face limitations due to the mildly acidic tumor microenvironment (TME) and scarce H2O2 availability. Aiming to overcome these hurdles, we report herein the preparation of copper-cobalt peroxide (CCp) nanoparticles, a novel catalyst that enables a pH-activated, self-supplying H2O2-mediated cascade reaction. In the slightly acidic TME (pH 6.5-7.0), CCp nanoparticles degrade, generating H2O2in situ. This intrinsic H2O2 production eliminates the need for external H2O2 sources and enables activation in a significantly higher pH range. Simultaneously, released Cu and Co ions, primarily in lower oxidation states, synergistically drive a catalytic loop for sustained hydroxyl radical (˙OH) production. The non-ferrous bimetallic approach exhibits exquisite pH sensitivity and self-sufficiency, surpassing traditional Fenton reactions. Comparative studies highlight CCp's superior performance against copper-based bimetallic peroxides containing Fe and Ce, confirming the synergistic power of Cu-Co pairing. In vitro experiments demonstrate that the synthesized CCp-NPs exhibit greater toxicity toward breast cancer cells (4T1) than towards non-cancerous cells, showcasing their therapeutic potential. Furthermore, CCp-NPs outperform other nanoparticles in inhibiting cancer cell proliferation, colony formation, and migration. Density Functional Theory (DFT) calculations suggest that Co doping enhances CCp's ability to participate in Fenton reactions. Overall, this work is pioneering in relation to the design of a new class of smart nanoparticles for CDT. The combination of self-generated H2O2, high pH activation, and synergistic metal effects in CCp opens the door for next-generation cancer theranostic nanoparticles with unprecedented efficiency and precision, minimizing side effects.

Chemistry Profile and Biological Activity of Campnosperma auriculatum Extracts

As our ongoing investigation for bioactive natural products from tropical plant, we performed preliminary study on one of important tropical plants in West Kalimantan, Terentang putih, Campnosperma auriculatum. The aims were to determine effective solvent used for extraction, chemistry profile, total phenolic content, free-radical scavenging, cytotoxicity, and anti-termite activities of leaves, stems, and roots extracts of C. auriculatum. Variation of solvent for extraction was selected based on its polarisation, namely, ethanol, ethyl acetate, and n-hexane. The effectiveness of solvent was determined by observing the rendemen of each extract, where amount of sample and solvent volume, duration of extraction, temperature, and maceration technique were controled. Determination of total phenolic content was performed using Folin-Ciocalteu method. IC50 value for free-radical scavenging activity was calculated by plotting standard concentration and absorption data observed through DPPH method. Cytotoxicity evaluation was performed to each ethanolic extract against 4T1 cancer cell line using MTT assay. Anti-termite activity was conducted against Coptotermes curvignathus by calculating percentage of termite mortality and paper weight loss. This research showed that ethanol solvent was the most effective extraction solvent giving the highest yield in each part of plant. Phytochemically, all extracts showed that they contain phenolics and alkaloids. Ethanolic extract of stems showed the highest total phenolic content with 737.6 ± 0.56 ppm (GAE) and the most active as free-radical scavenger with IC50 value of 135.51 ± 0.91 ppm. Meanwhile, the roots extract exhibited pronounce cytotoxicity toward 4T1 cancer cell line with IC50 value of 1.55 ± 3.29 µg/ml and high selectivity index. Furthermore, the roots extract displayed most active as anti-termite as well as antifeedant. Hitherto, this study is the first report on phytochemistry and biological activity from leaves, stems, and roots of C. auriculatum. Moreover, this plant can be explored further for its potential on medicinal and agricultural industries.

Development of folic acid functionalized bilosomes for delivery of vorinostat to breast cancer cells: Characterization and cytocidal effects on MCF-7 and 4T1 breast cancer cell lines

Purpose: Breast cancer is a prevalent form of cancer in woman. Vorinostat (VOR) is a chemotherapeutic drug that has been utilized for treatment of breast cancer, but its effectiveness is limited due to low bioavailability and several side effects. The primary aim of this study is to prepare folic acid (FA) conjugated pegylated bilosomes containing VOR for the selective targeting of breast cancer cells with the FA receptor expression. Accordingly, lithocholic acid (LCA) was used as a bile acid in bilosomes due to its anti-cancer and anti-proliferation effects. Methods: VOR loaded bilosomes were prepared using the thin-film hydration method and optimized by applying two-level fractional factorial design. Various properties of the considered bilosomes, including particle size, zeta potential (ZP), polydispersity index (PdI), encapsulation efficiency (EE) % and drug loading (DL) %, were then investigated and synthesized FA-PEG-Cholesterol was incorporated in the optimized bilosomes. The anti-cancer efficacy of VOR loaded FA-PEG- bilosomes was also evaluated in vitro using the MCF-7 and 4T1 breast cancer cell lines. Furthermore, drug-free FA-PEG-bilosomes and bilosomes were evaluated for biocompatibility in the L929 cell line. Results: The optimized VOR loaded bilosomes exhibited spherical particles with the size of 305.33 ± 18.50 nm, PdI of 0.37 ± 0.03, zeta potential of -17.66 ± 0.15 mV, EE of 92.91 ± 0.22 % and DL% of 23.64 ± 0.04%. Incorporation of FA-PEG-cholesterol in nanobilosomes increased the particle size and absolute value of zeta potential. In vitro cytotoxicity study also revealed that VOR loaded FA- PEG-bilosomes demonstrated a greater cytotoxic effect, as compared to the free VOR and VOR- bilosomes in both MCF-7 and 4T1 cancer cells. Conclusion: This showed that FA- PEG-bilosomes could be a promising formulation for the treatment of FA (+) tumors.

Tetramethyl Cucurbit[6]uril-Porphyrin Supramolecular Polymer Enhances Photosensitization.

Porphyrins serve as photosensitizers (PS) in the realm of cancer photodynamic therapy (PDT). Upon excitation by laser light, porphyrins are capable of converting molecular oxygen into highly cytotoxic singlet oxygen (1O2). However, the rigid π-conjugated structure of porphyrins frequently results in the formation of aggregates in aqueous solutions, which leads to the self-quenching of the excited state. Cucurbit[n]urils exhibit the capacity to stably bind with porphyrins via host-guest interactions, effectively inhibiting their aggregation and potentially enhancing the therapeutic efficacy of PDT. In this study, water-soluble tetramethyl cucurbit[6]uril (TMeQ[6]) was selected as the host, while four propionic acid group-appended porphyrin cationic (TPPOR) was utilized as guests to construct a supramolecular photosensitizer (TPPOR-2TMeQ[6]) in a molar ratio of 2:1. Further experimental findings demonstrate that the presence of TMeQ[6] inhibits the aggregation of TPPOR through non-covalent interactions. This inhibition reduces the energy difference between the excited singlet and triplet states, thereby enhancing the conversion efficiency of 1O2. Moreover, TPPOR-2TMeQ[6] exhibits favorable biocompatibility and minimal dark toxicity against breast cancer cells (4T1). Upon intracellular excitation, the levels of reactive oxygen species (ROS) significantly increase, inducing oxidative stress in 4T1 cells and leading to apoptosis. Consequently, the findings of this study suggest that the enhanced photosensitization achieved through this supramolecular approach is likely to promote the anticancer therapeutic effects of PDT, thereby broadening the application prospects of porphyrins within PDT systems.

Loss of MK2 Enhances Radiation-Mediated Apoptosis in Bladder Cancer.

Bladder cancer patients unable to receive cystectomy or who choose to pursue organ-sparing approach are managed with definitive (chemo)radiotherapy. However, this standard of care has not evolved in decades and disease recurrence and survival outcomes remain poor. Identifying novel therapies to combine with radiotherapy (RT) is therefore paramount to improve overall patient outcomes and survival. One approach is to find cellular mechanisms that can be targeted to increase the radiosensitivity of bladder cancer. The stress-activated kinase directly downstream from p38 mitogen-activated protein kinase (MAPK), mitogen-activated protein kinase activated protein kinase 2 (MAPKAPK2 or MK2), has been shown to enhance cancer-mediated inflammation, mesenchymal gene expression, and in vivo tumor growth. Here we examined the impact that MK2 knockdown (KD) has on bladder cancer cell radiosensitivity. We utilized short hairpin RNA (shRNA) KD of MK2 using lentiviral transfection in the bladder cancer cell lines, T24 and HTB9. We compared the growth of KD cells to wild type using colony formation assays, proliferation assays and cell counts to determine differences in cell growth. Apoptosis was examined by annexin-based flow cytometry and western blots. Flow cytometry was also used for cell cycle analysis. KD clones showed a greater than 90% inhibition of MK2 expression as determined by western blot. Clonogenic assays exhibited an increase in radiosensitivity among the MK2 KD bladder cancer cells. These data were supported with proliferation assays that displayed a greater reduction in cell number following RT in MK2 KD bladder cancer cells. Annexin V binding in bladder cancer cells suggested increased apoptosis in MK2 KD cells. This was confirmed by comparing the amount of cleaved caspase products for the caspases 3 and 8 to scrambled control (SCR), and the release of cytochrome C into the cytosol. Both cell types showed disruptions in the cell cycle but at different points in the cycle. These results show that MK2 controls irradiation-induced apoptosis in bladder cancer cells.

Synthesis, characterisation, single crystal structure and evaluation of a redox innocent carbazate functionalized phenanthroline for antimycobacterial and anticancer activity

Development of bioactive candidates for cancer and bacterial infections are ever demanding challenges due to the resistance shown by these cancer and bacterial cells for already exposed drug molecules. Methyl carbazate derivatized phenanthroline compound 6-[2-(methoxycarbonyl)diazen-1-yl]-1,10-phenanthroline-5-one (MCDPO) is synthesized in a three step reaction from 1,10-phenanthroline. The spectroscopic features of MCDPO are studied by HRMS, IR, 1H NMR and 13C NMR, UV-visible spectroscopy. The three-dimensional molecular structure of the MCDPO is confirmed by single crystal XRD study. The MCDPO crystallized in a triclinic system P-1 space group with the following unit cell parameter: a = 5.0347(2) Å, b = 10.3509(4) Å, c = 11.8816(4) Å, α = 84.431(3)°, β = 84.172(3)°, γ = 81.380(4)°, and V = 606.92(4) Å3 at T = 133 K. The MCDPO is containing aromatic rings, hydrogen bonding donors as well as hydrogen bonding acceptor groups forming supramolecular molecular arrangements through C-H⋯O, CH⋯N, C-O⋯C, π-π and π⋯C non-covalent interactions. Electrochemical redox and electrochromic features of MCDPO are studied through cyclic voltammetry and UV-vis based spectroelectrochemistry. This compound shows good anticancer activity with IC50 values 1.438, 6.576 and 2.901 µM against 4T1, MCF-7 and PC-3 cancer cell lines respectively. The flow cytometry study on 4T1 cells suggests that the MCDPO promoted cancer cell death by inducing apoptosis, and cell cycle arrest in the G0/G1 phase. It also induces nuclear fragmentation and reactive oxygen species (ROS) generation, which was studied by DAPI, AO, and DCFH-DA based cellular staining studies by fluorescence confocal imaging. The MCDPO also studied for antibacterial activity against Escherichia Coil bacteria and Mycobacterium tuberculosis (Mtb). The MCDPO shows minimum inhibitory concentration (MIC) of 0.39 µg/mL against Mtb which is slightly better than the one of the clinically used drug candidates Ethambutol.

Inhibition of Aβ Aggregation and Tau Phosphorylation with Functionalized Biomimetic Nanoparticles for Synergic Alzheimer's Disease Therapy.

The main pathological mechanisms of Alzheimer's Disease (AD) are extracellular senile plaques caused by β-amyloid (Aβ) deposition and intracellular neurofibrillary tangles derived from hyperphosphorylated Tau protein (p-Tau). However, it is difficult to obtain a good curative effect because of the poor brain bioavailability of drugs, which is attributed to the blood-brain barrier (BBB) restriction and complicated brain conditions. Herein, HM-DK was proposed for synergistic therapy of AD by using hollow mesoporous manganese dioxide (HM) as a carrier to deliver an Aβ-inhibiting peptide and a Dp-peptide inhibitor of Tau-related fibril formation synergistically. Inspired by 4T1 cancer cells promoting BBB penetration during brain metastasis, a prospective biomimetic nanocarrier (HM-DK@CM) encapsulated by 4T1 cell membranes was designed. After crossing the BBB, HM-DK@CM inhibited Aβ aggregation and prevented Tau phosphorylation simultaneously. Moreover, by taking advantage of the catalase-like activity of HM, HM-DK@CM relieved oxidative stress and altered the microenvironment associated with the development of AD. Compared with the single therapeutic drug, HM-DK@CM restored nerve damage and improved AD mice's learning and memory abilities by decreasing Aβ oligomer, p-Tau protein, and inflammation through various pathways for synergistic therapy, which has broad prospects for the effective treatment of AD.

Effective Synthesis of C20-Epi-Isothiocyanato-Salinomycin and its Thiourea Derivatives as Potential Anticancer Agents.

Salinomycin, a naturally occurring polyether ionophore antibiotic isolated from Streptomyces albus, has been demonstrated potent cytotoxic activity against a variety of cancer cell lines. In particular, it exhibits selective targeting of cancer stem cells. However, systemic toxicity, drug resistance and low bioavailability of the drug significantly limit its potential applications. In this study, the C20-epi-isothiocyanate of salinomycin was designed and synthesized, and then reacted with amines as a versatile synthon to assemble a series of salinomycin thiourea derivatives, which improved the druggability of salinomycin. The antiproliferative activities of the compounds were evaluated in vitro against A549, HepG2, HeLa, 4T1, and MCF-7 cancer cell lines using the CCK-8 assay. The pharmacological results showed that some salinomycin thiourea derivatives exhibited excellent inhibitory activity against at least one of the tested tumor cells and high selectivity. Further mechanistic studies showed that compound 9 f, containing a 3,5-difluorobenzyl moiety, could directly induce apoptosis, probably by increasing caspase-9 protein expression and cell cycle arrest in G1 phase in a concentration dependent manner.

CRH upregulates supervillin through ERK and AKT pathways to promote bladder cancer cell migration.

Corticotropin-releasing hormone (CRH) has been well documented playing a role in the regulation of cellular processes, immune responses, and inflammatory processes that can influence the occurrence and development of tumors. Supervillin (SVIL) is a membrane-associated and actin-binding protein, which is actively involved in the proliferation, spread, and migration of cancer cells. This work investigated CRH's influence on bladder cancer cells'migration and relevant mechanisms. By using human bladder cancer cells T24 and RT4 in wound healing experiments and transwell assay, we found that the migration ability of the T24 cells was significantly increased after CRH treatment. In vivo experiments showed that CRH significantly promoted the metastases of T24 cells in cell line-derived xenograft (CDX) mouse model. Interestingly, downregulation of SVIL by SVIL-specifc small hairpin RNAs significantly reduced the promoting effect of CRH on bladder cancer cell migration. Furthermore, CRH significantly increased SVILmessenger RNA and protein expression in T24 cells, accompanied with AKT andERK phosphorylation in T24 cells. Pretreatment with AKT inhibitor (MK2206) blocked the CRH-induced SVIL expression and ERK phosphorylation. Also, inhibition of ERK signaling pathway by U0126 significantly reduced the CRH-induced SVIL expression and AKT phosphorylation. It suggested that cross-talking between AKT and ERK pathways was involved in the effect of CRH on SVIL. Taken together, we demonstrated that CRH induced migration of bladder cancer cells, in which AKT andERK pathways -SVIL played a key role.

Transcriptome profiling of Canine Parvovirus 2 Nonstructural gene 1(CPV2.NS1) transfected 4T1 mice mammary tumor cells to elucidate its oncolytic effects

Oncolytic viral gene therapy is a directed approach to target cancer cells without affecting healthy cells of the body. Canine parvovirus (CPV2) is an oncolytic virus that precisely targets and destroys neoplastic cells by causing DNA damage, mitochondrial damage, and apoptosis. Non-structural gene 1 (NS1) of CPV, concerned with viral DNA replication is a key mediator of cytotoxicity of CPV and can specifically cause tumor cell lysis. In the present study, by using the transcriptomics approach, we tried to identify molecular pathways and key genes involved in CPV2.NS1 mediated 4T1 mice mammary tumor cell death. We identified necroptosis and mitochondrial damage-mediated apoptosis as major cell death pathways leading to CPV2.NS1 transfected 4T1 cancer cell death. Various DEGs identified in our study play an important role in pathways like the PI3K/AKT pathway, diverse metabolic pathways, MAPK signaling pathway, and FGF signaling pathway, whichare mostly dysregulated in cancerous conditions. Histone variant H2A.X genes, Capn2, and Mapk10/JNK are predicted as key genes that play a role in causing endoplasmic reticulum stress and mitochondrial damage, thereby leading to necroptosis and apoptosis. This study is a preliminary work done to identify key genes and molecular pathways involved in CPV2.NS1 mediated 4T1 cancer cells death which need to be further validated to establish this viral gene as a potent oncolytic agent.

Prognostic and therapeutic implications of tumor-restrictive type III collagen in the breast cancer microenvironment

Collagen plays a critical role in regulating breast cancer progression and therapeutic resistance. An improved understanding of both the features and drivers of tumor-permissive and -restrictive collagen matrices are critical to improve prognostication and develop more effective therapeutic strategies. In this study, using a combination of in vitro, in vivo and bioinformatic experiments, we show that type III collagen (Col3) plays a tumor-restrictive role in human breast cancer. We demonstrate that Col3-deficient, human fibroblasts produce tumor-permissive collagen matrices that drive cell proliferation and suppress apoptosis in non-invasive and invasive breast cancer cell lines. In human triple-negative breast cancer biopsy samples, we demonstrate elevated deposition of Col3 relative to type I collagen (Col1) in non-invasive compared to invasive regions. Similarly, bioinformatics analysis of over 1000 breast cancer patient biopsies from The Cancer Genome Atlas BRCA cohort revealed that patients with higher Col3:Col1 bulk tumor expression had improved overall, disease-free, and progression-free survival relative to those with higher Col1:Col3 expression. Using an established 3D culture model, we show that Col3 increases spheroid formation and induces the formation of lumen-like structures that resemble non-neoplastic mammary acini. Finally, our in vivo study shows co-injection of murine breast cancer cells (4T1) with rhCol3-supplemented hydrogels limits tumor growth and decreases pulmonary metastatic burden compared to controls. Taken together, these data collectively support a tumor-suppressive role for Col3 in human breast cancer and suggest that strategies that increase Col3 may provide a safe and effective therapeutic modality to limit recurrence in breast cancer patients.

Alginate-functionalized and 4T1 cell membrane-coated multi-tasking nanoparticulate system for near-infrared-triggered photodynamic therapy on breast cancer: In vitro cellular and in vivo mice models

Recently, combination treatment of chemo-dynamic therapy (CDT) and photodynamic therapies (PDT) is well-known and prominent therapeutic strategy for breast tumor. Importantly, tailored nanomedicines with unique personalized properties including nanocarrier suitability and effective targeting ability that requires the exhaustive understanding of tumor microenvironment. Recently, researchers have designed a smart upconversion nanoparticles (UCNPs) that have unique characteristics to achieve targeting for respond tumor microenvironment. In the present study, we first time fabricated a novel combination of oxidized sodium alginate-enveloped and 4T1 cancer cell membrane-coated up-conversion nanoparticles (4TUCNP@SMZ) were engineered for breast cancer-targeted therapy. The nanoparticles could be formed via electrostatic interaction, which showed excellent biocompatibility, increased cellular uptake with normal and cancer cells. The fabricated Alginate and 4T1-membrane functionalized up-conversion nanoparticles significantly benefitted to targeted delivery system for local breast cancer and prominently inhibit tumor development via chemo-dynamic therapy (CDT) and PDT. The greater susceptibility of tumor cells to oxidative stress may also result from the depletion of intracellular GSH by the 4TUCNP@SMZ nanoparticles. The in vitro cell models (4T1 and MCF-7), in vivo tumor model and histological observation demonstrated that 4TUCNP@SMZ nanoparticles effectively targeted to breast tumor microenvironment and inhibit breast cancer cells. This report suggested that multifunctional Alginate-functionalized nanoparticles are a versatile agent for phototherapy for breast cancer treatment.

Enhanced anti-tumor efficacy of S3I-201 in breast cancer mouse model through Wharton jelly- exosome

ObjectiveExosomes, membrane-enveloped vesicles found in various cell types, including Wharton’s jelly mesenchymal stem cells, play a crucial role in intercellular communication and regulation. Their use as a cell-free nanotechnology and drug delivery system has attracted attention. Triple-negative breast cancer (TNBC) is a major global health problem and is characterized by a high mortality rate. This study investigates the potential of Wharton’s Jelly mesenchymal stem cell-derived exosomes (WJ-Exo) as carriers of S3I-201 and their effects on STAT3 expression in breast cancer cell lines, and evaluates whether these exosomes can enhance the anti-tumor effect of S3I-201.MethodsThe filtered WJ-Exos were analyzed by Transmission Electron Microscopy (TEM), Scanning electron microscopy (SEM), Dynamic Light Scattering (DLS), flow cytometry, and Western blotting. These exosomes were then used for loading with S3I-201, resulting in the nano-formulation WJ-Exo(S3I-201). The effect of WJ-Exo(S3I-201) on 4T1 cancer cells was investigated in vitro using MTT assay, flow cytometry, wound healing assay, Western blotting and Quantitative Real-Time Polymerase chain reaction (qPCR) analysis. Finally, the therapeutic efficacy of the nano-formulation was investigated in vivo using a tumor-bearing mouse model.ResultsIn vitro experiments showed that co-incubation of 4T1 cells with the nano-formulation resulted in a significant reduction in p-STAT3 levels, induction of apoptosis, modulation of Bcl-2, Bax and caspase-3 protein and gene expression, and inhibition of migration. In vivo, treatment of tumor-bearing mice with WJ-Exo(S3I-201) showed a strong antitumor effect that exceeded the efficacy observed in the S3I-201 group.ConclusionOur results demonstrate that WJ-Exo is an effective carrier for targeting S3I-201 to tumor cells and enhances the therapeutic efficacy of S3I-201 in tumor-bearing mice.

Glutathione-responsive biodegradable nanohybrid for cancer photoacoustic imaging and gas-assisted photothermal therapy

Photothermal therapy (PTT), particularly in the near-infrared-II (NIR-II) range, has attracted widespread attention over the past years. However, the accompanied inflammatory responses can result in undesirable side effects and contribute to treatment ineffectiveness. Herein, we introduced a novel biodegradable nanoplatform (CuS/HMON-PEG) capable of PTT and hydrogen sulfide (H2S) generation, aimed at modulating inflammation for improved cancer treatment outcomes. The embedded ultrasmall copper sulphide (CuS) nanodots (1–2 nm) possessed favorable photoacoustic imaging (PAI) and NIR-II photothermal capabilities, rendering CuS/HMON-PEG an ideal phototheranostic agent. Upon internalization by 4T1 cancer cells, the hollow mesoporous organosilica nanoparticle (HMON) component could react with the overproduced glutathione (GSH) to produce H2S. In addition to the anticipated photothermal tumor ablation and H2S-induced mitochondrial dysfunction, the anti-inflammatory regulation was also been demonstrated by the downregulation of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1β). More importantly, the modulation of inflammation also promoted wound healing mediated by PTT. This work not only presents a H2S-based nanomodulator to boost NIR-II PTT but also provides insights into the construction of novel organic/inorganic hybrid nanosystems.

Construction of CXCR4 Receptor-Targeted CuFeSe2 Nano Theranostic Platform and Its Application in MR/CT Dual Model Imaging and Photothermal Therapy.

Targeting, imaging, and treating tumors represent major clinical challenges. Developing effective theranostic agents to address these issues is an urgent need. We introduce an "all-in-one" tumor-targeted theranostic platform using CuFeSe2-based composite nanoparticles (CuFeSe2@PA) for magnetic resonance (MR) and computed tomography (CT) dual model imaging-guided hyperthermia tumor ablation. Plerixafor (AMD3100) is bonded to the surface of CuFeSe2 as a targeting unit. Due to the robust interaction between AMD3100 and the overexpressed Chemokine CXC type receptor 4 (CXCR4) on the membrane of 4T1 cancer cells, CuFeSe2@PA specifically recognizes 4T1 cancer cells, enriching the tumor region. CuFeSe2@PA serves as a contrast agent for T2-weighted MR imaging (relaxivity value of 1.61 mM-1 s-1) and CT imaging. Moreover, it effectively suppresses tumor growth through photothermal therapy (PTT) owing to its high photothermal conversion capability and stability, with minimized side effects demonstrated both in vitro and in vivo. CuFeSe2@PA nanoparticles show potential as dual-mode imaging contrast agents for MR and CT and provide an effective means of tumor treatment through photothermal therapy. The surface modification with Plerixafor enhances the targeting ability of the nanoparticles, performing more significant efficacy and biocompatibility in the 4T1 cancer cell model. The study demonstrates that CuFeSe2@PA is a promising multifunctional theranostic platform with clinical application potential.

Investigating the effect of resveratrol on the survival rate of 4T1 breast cancer cells by MTT method

Cancer is known as an incurable, deadly and deadly disease with pain and disability. During recent decades, changes in people's lifestyles have increased the incidence and prevalence of breast cancer worldwide. With the wide spread of this disease, research has also increased on this issue. Resveratrol is known as a natural polyphenol found in red grapes and some other foods, and with its important anti-cancer properties, it can be effective in reducing the risk of breast cancer and its treatment. Research has shown that resveratrol can have positive effects on breast cancer by reducing DNA methylation, reducing cell proliferation, and reducing cancer growth factors. In this research, resveratrol has been used against 4T1 cancer cells, which were treated with different concentrations of resveratrol after cultivation in 96-well plates and measured by the MTT method. The obtained results showed that resveratrol in all concentrations and at different times significantly reduces the survival of 4T1 cancer cells. By increasing the concentration and treatment time, the decrease in cell viability increases. This indicates strong, dose- and time-dependent effects of resveratrol on breast cancer cells.

Quality by design approach of apocynin loaded clove oil based nanostructured lipid carrier as a prophylactic regimen in hemorrhagic cystitis in vitro and in vivo comprehensive study

Apocynin (APO) is a naturally occurring acetophenone with eminent anti-inflammatory and anti-oxidant peculiarities. It suffers from poor bioavailability due to low aqueous solubility. Herein, APO was loaded in a Clove oil (CO) based Nanostructured lipid carrier (NSLC) system using a simple method (ultrasonic emulsification) guided by a quality-by-design approach (23 full factorial design) to optimize the formulated NSLCs. The prepared NSLCs were evaluated regarding particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE%). The optimal formula (F2) was extensively investigated through transmission electron microscope (TEM), Fourier transform infrared (FT-IR) spectroscopy, Differential scanning calorimetry (DSC), X-ray diffractometry (XRD), in vitro release, and stability studies. Cytotoxicity against human urinary bladder carcinoma (T24) cell line and in vivo activity studies in rats with induced cystitis were also assessed. The results disclosed that the optimal formula (F2) had PS of 214.8 ± 5.8 nm with EE% of 79.3 ± 0.9%. F2 also exhibited a strong cytotoxic effect toward the T24 cancer cells expressed by IC50 value of 5.8 ± 1.3 µg/mL. Pretreatment with the optimal formula (orally) hinted uroprotective effect against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rat models, emphasized by histopathological, immunohistochemical, and biochemical investigations. In consideration of the simple fabrication process, APO-loaded CO-based NSLCs can hold prospective potential in the prophylaxis of oncologic and urologic diseases.

A new isoprenyl-phenol-type meroterpenoid from mangrove endophytic fungus Aspergillus sp. GXNU-Y65

Asperphenol A (1), a new isoprenyl-phenol-type meroterpenoid, was isolated from the mangrove endophytic fungus Aspergillus sp. GXNU-Y65 together with five known compounds (2-6). All structures were assigned using extensive NMR spectroscopic data and electronic circular dichroism (ECD) calculations. Compounds 1-6 were evaluated for their cytotoxic activity against A549 and T24 human cancer cell lines. Among them, compounds 1 and 5 exhibited moderate inhibitory activities against T24 cancer cell lines with the IC50 values of 26.71 and 43.50 μM, respectively.

MIGRATION INHIBITION ACTIVITY BY METHANOL EXTRACT Hibiscus tiliaceus Linn. ON 4T1 BREAST CANCER

The prevalence of breast cancer cases in Indonesia is increasing along with the ability of cancer cells to migrate or move from the primary tumor mass and form new colonies elsewhere. The migration of cancer cells has encouraged the develop anticancer drugs from natural ingredients. Waru leaves have been shown to have cytotoxic activity. This study aims to determine the inhibition activity of migration of breast cancer cells 4T1 from methanol extract of waru leaves. Waru leaves methanol extract was obtained using the maceration method. Cytotoxic test of methanol extract of waru leaves (MEWL) was the migration test used in the scratch wound healing method at concentrations 162.5, 325, and 650 μg/mL at 0, 18, 24, and 42 hours after treatment. Analysis of IC50 using linear regression, while large areas were analyzed using Image-J software. The percentage of data closure was analyzed statistically with the Anova Repeated Measure test. All concentrations of Methanol Extract of Waru Leaves had significant inhibition of cell migration (p<0,05) compared to control at each observation time at 0, 18, 24, and 42 hours after treatment. So, MEWL is able to inhibit migration in 4T1 cells