This study evaluated the clinical characteristics and treatment outcomes of bigger premature infants treated for retinopathy of prematurity (ROP).

Indocyanine green (ICG) demonstrates both photodynamic therapy (PDT) and photothermal therapy (PTT) capabilities but faces challenges including rapid blood clearance, insufficient ROS production, and molecular chaperone-induced thermotolerance. However, highly efficient synchronous targeting delivery of photosensitizer and sensitizer to cancer cells remains a giant challenge due to their significantly different physicochemical properties. To address these limitations, we developed a dual-responsive nano-platform, TCS-βCD@CLRP/PEI-SS@ICG-NPs (I&C-NPs), designed for ICG and chloramphenicol (CLRP) co-delivery and cascade synergetic anti-tumor effect through mitochondrial destruction/photothermal therapy/photodynamic therapy (Mito destruction/PTT/PDT). Mitochondrial-targeted "pocket" cyclodextrin-grafted carboxymethyl chitosan (TCS-βCD) and biodegradable disulfide-grafted polyethyleneimine (PEI-SS) were designed and synthesized. Mitochondrial respiration consumes oxygen in cells like "oxygen consumption for fire", while CLRP, the "fire extinguisher", can inhibit mitochondrial respiration and reduce oxygen consumption. Through multiple intermolecular forces, PEI-SS and TCS-βCD encapsulated ICG with 71.05 % efficiency and CLRP with 78.18 % efficiency, forming I&C-NPs exhibiting 123.5 nm in size and exhibiting a zeta potential of +7.8 mV. These nanoparticles functioned as "On-call firefighter", targeting mitochondria through dual responsiveness to elevated glutathione (GSH) in the tumor microenvironment (TME) and laser-induced photothermal heating. The system achieved GSH-/laser-activated drug release efficiency of >80 % and efficient cascade synergetic anti-tumor efficacy: (1) I&C-NPs target and disrupt the mitochondria of tumor cells, and CLRP acts as a PDT sensitizer to minimize oxygen consumption. (2) The PDT effect can be amplified, generating large amounts of ROS (1.69-fold compared to free ICG) in vivo and showing a reduction of HIF-1α. (3) The production of ROS disrupts heat shock proteins and down-regulates HSP 70 protein expression, decreasing tumor tolerance to hyperthermia and resulting in robust photothermal conversion efficiency. Consequently, GSH-/laser-activated mitochondria-oriented I&C-NPs could co-deliver ICG and CLRP, achieving the cascade synergetic anti-tumor effect of Mito destruction/PTT/PDT with the tumor inhibitory rate > 77 %.

Inositol-requiring enzyme 1α (IRE1α) signaling is one of three arms of the unfolded protein response, playing a vital role in maintaining endoplasmic reticulum homeostasis. Pharmacological modulation of this pathway offers potential therapeutic strategies for various diseases. Molecular glues may regulate protein stability and activity by inducing protein-protein interaction. Here, we find that verteporfin functions as a molecular glue, promoting IRE1α dimerization and activation. Specifically, verteporfin binds to IRE1α, facilitating its dimerization, which relies on the His692 residue. This activation of IRE1α triggers XBP1 splicing and miR-153-mediated downregulation of PTEN, along with AKT phosphorylation. Additionally, we identify the pro-metastasis gene BACH1 as a novel target of miR-153, which is downregulated by IRE1α and verteporfin. While verteporfin inhibits breast cancer cell viability and invasion, its combination with an AKT inhibitor synergistically suppresses breast cancer progression. Our findings establish a mechanistic link between IRE1α and PI3K/AKT signaling, highlighting a possibility for therapeutic intervention.

Cholangiocarcinoma (CCA) often exhibits poor responses to chemotherapy due to mechanisms of chemoresistance (MOCs). The Wnt/β-catenin pathway, hyperactivated in CCA and crucial for cell proliferation, migration, and angiogenesis, may contribute to CCA chemoresistance. This study investigates the role of Wnt/β-catenin in CCA multidrug resistance phenotype and explores the therapeutic potential of combining chemotherapy with Wnt/β-catenin inhibitors.

Obesity is linked to a heightened risk of developing triple-negative breast cancer (TNBC). Obesity-associated triple-negative breast cancer (OA-TNBC) presents limited therapeutic options and is characterized by a poor prognosis. Although Astragaloside IV (ASIV) exhibits anti-tumor properties across different cancers, its effect and mechanisms in OA-TNBC remain unclear.

Angiosarcoma is a rare and aggressive malignancy with limited treatment options. This phase II, multicenter, open-label, single-arm study (AngioCheck) evaluated the efficacy and safety of nivolumab in patients with cutaneous angiosarcoma previously treated with taxane-based chemotherapy.

Cancer remains one of the leading causes of global mortality, necessitating novel therapeutic strategies. Liver X Receptors (LXRα and LXRβ) and the Farnesoid X Receptor (FXR) are nuclear receptors that regulate lipid and cholesterol homeostasis, bile acid metabolism, inflammation, and immune response pathways intricately linked to cellular dysregulation in oncogenesis. Despite their therapeutic potential, these receptors remain underexplored targets in cancer research. This study implements an extensive suite of computational strategies to identify and evaluate potential modulators of LXRα/β and FXR, through virtual screening using resveratrol as the lead scaffold, followed by drug-likeness evaluation and toxicity profiling. Molecular docking (MVD, AutoDock and ML-PLIC) identified C144 (AZD7762), a well-established CHK1 kinase inhibitor, as the top-ranked ligand, demonstrating superior binding affinity and conformational stability via convergent interaction mechanisms. Additionally, reactivity descriptors derived from density functional theory (DFT) and frontier molecular orbital (FMO) analyses further substantiated its favorable electronic properties and chemical stability. Structural pharmacophore mapping using LigandScout confirmed pharmacophoric alignment with receptor active sites, while bioactivity profiles predicted high efficacy. Extensive quantum mechanical analyses (MEP, NBO, Mulliken/NPA, NCI, RDG, ELF, LOL, BSA, HAS) revealed favorable electronic characteristics, stability, charge distribution, and interaction potential. CLC-Pred, biotransformation (RA), pharmacokinetic profiling, molecular dynamics simulations, MM/PBSA and Shermo-based thermodynamic predictions further validated its biostability and systemic compatibility. These findings position C144 (AZD7762) as a promising anticancer candidate targeting LXRα, LXRβ, and FXR pathways. Further optimization and validation through in vitro and in vivo studies are essential for advancing these findings toward clinical application.

Drug efflux mediated by transporter proteins is one of the major mechanisms conferring multidrug resistance (MDR) to antimicrobial agents in bacteria and to chemotherapeutics in cancer cells. Therefore, the development or identification of efflux modulators represents a promising strategy to overcome the resistant phenotype. Various chemical compounds have been tested in experimental studies as reversal agents either in combination with antimicrobial or anticancer drugs and have shown sensitizing activity in resistant bacteria or cancer cell lines. Owing to the common resistance mechanisms exhibited by bacteria and cancer cells, the identification of chemical agents with dual reversal activity offers a strategy to simultaneously combat antibacterial and cancer multidrug resistance.

The dense extracellular matrix (ECM) of stroma-rich solid tumors acts as a significant barrier to effective chemotherapy by hindering drug penetration. In this study, a supramolecular hydrogel was successfully developed, enabling the codelivery and sequential release of hydrophilic and lipophilic drugs designed to target the ECM. The hydrogel is easy to prepare, has self-healing properties and excellent biocompatibility. Upon administration, the hydrogel first releases pirfenidone to inhibit collagen production, weakening the ECM, followed by the release of paclitaxel, which improves tumor penetration. The effectiveness of this sequential drug delivery system was validated in both oral squamous cell carcinoma and pancreatic cancer models, a classic example of a tumor with abundant ECM. In vitro experiments showed controlled sequential release profiles, whereas in vivo experiments using cell-derived and patient-derived xenograft models revealed that the hydrogel was more effective at tumor suppression compared to traditional methods. Single administration of the hydrogel led to long-term localized drug release, maintaining higher concentrations of chemotherapeutic agents in the tumor tissue and effectively reducing the tumor volume. This study provided a promising strategy to enhance chemotherapy in ECM-dense tumors, offering an efficient and minimally invasive method for localized, sustained-release cancer therapy.

This study reports the multifunctional potential of gold nanoparticles (AuNPs) biosynthesized by using Salvia splendens leaf extract (SSLE). The biosynthesized AuNPs were characterized by UV-Visible spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering, followed by the assessment of their anti-cancer, anti-oxidant, anti-inflammatory and anti-bacterial potentials. The biosynthesized SSLE-AuNPs showed a characteristic absorbance peak at 559 nm that corresponds to the surface plasmon resonance (SPR) band of the AuNPs. The zeta potential of SSLE-AuNPs was estimated to be ‒ 21 ± 1.9 mV, and TEM analysis confirmed the particles to be spherical with an average size of 94.8 ± 5.1 nm. The SSLE-AuNPs exhibited dose-dependent antioxidant activity, with IC50 values of 218.5 ± 4.2 µg/mL (DPPH) and 185.3 ± 3.7 µg/mL (ABTS), compared to ascorbic acid (32.1 ± 1.8 µg/mL and 28.6 ± 1.5 µg/mL, respectively. In addition, SSLE-AuNPs exerted potent anti-bacterial effect against Staphylococcus aureus (MIC50 68 ± 2.1 μg/mL) and Klebsiella pneumoniae (MIC50 82 ± 2.3 μg/mL), which was comparable to that of the standard antibacterial agent, tetracycline. Moreover, SSLE-AuNPs induced significant reduction in cellular viability of A549 cells at concentrations of 100, 200 and 400 μg/mL, respectively (p < 0.001). Such cytotoxic potential of SSLE-AuNPs was accompanied by considerable instigation of nuclear fragmentation and condensation, caspase activation, and ROS generation in A549 cells. Furthermore, in vitro studies highlighted the anti-inflammatory potential of SSLE-AuNPs on murine alveolar macrophages (J774A.1) via deflating inflammatory mediators such as the proinflammatory cytokines. To sum up, the present findings have substantiated the antioxidant, antibacterial, anticancer and antiphlogistic properties of SSLE-AuNPs, paving the way for subsequent investigations into green synthesized nano-formulations.

Patients with disseminated metastatic disease from breast cancer are likely to have liver involvement in >50% of cases at some point during disease progression. These patients have a poor prognosis; and, when treated with the standard of care systemic therapy they have a median survival of <9-months. Increasing survival in breast cancer patients will likely require the administration of better therapies that are specifically targeted to treat distant metastases. One approach to increasing treatment efficacy for breast cancer liver metastases is through the application locoregional therapies. Locoregional therapies are an appealing interventional approach for breast cancer patients with liver metastases since these tumor lesions are accessible via minimally invasive procedures that can be administered using either ultrasound or CT imaging. Current locoregional therapies to treat breast cancer liver metastases are non-specific and have not produced significant increases in survival. The goal of this study was to design and test a targeted locoregional therapeutic intervention for breast cancer liver metastases. The lead candidate, a fixed-dose small-molecule drug called MBC-005, was tested in vitro and then the efficacy was evaluated in a BALB/c mouse liver metastases model. A novel formulation of N-allyl noroxymorphone hydrochloride incorporated into an alginate-based gel overcomes many of the limitations associated with the administration of small-molecule drugs, which include solubility, off-target toxicity, and enzymatic degradation. In vitro results demonstrated that MBC-005 mediated its anti-tumorigenic effect through a p21-dependent mechanism via a novel molecular pathway, in which N-allyl noroxymorphone component of MBC-005 stimulated the opioid growth factor receptor to increase p21 expression. Intratumoral administration of MBC-005 increased survival 3.9-fold in mice and significantly decreased tumor volume 4-fold. While many cytotoxic therapies increase p21 expression as a response to DNA damage, MBC-005 increased p21 expression independent cytotoxic DNA damage. MBC-005 did not induce off-target toxicity; and, as such, would be amenable to multiple rounds of administration. Nevertheless, it is notable that the positive effects of MBC-005 treatment on increasing survival and decreasing tumor volume in mice was achieved using a single dose.

Despite advancements in treatment for B-cell non-Hodgkin lymphoma (B-NHL) in recent decades, many patients still relapse or are refractory to treatment, which represents a high unmet medical need. Novel CD20 × CD3 T-cell-engaging bispecific antibodies (bsAbs) have created a new paradigm for the treatment of B-NHL. Pivotal studies of four CD20 × CD3 bsAbs, mosunetuzumab, glofitamab, epcoritamab, and odronextamab, as monotherapy, have demonstrated robust responses with generally manageable safety profiles in patients with relapsed or refractory follicular lymphoma and diffuse large B-cell lymphoma after ≥ 2 lines of systemic therapy. These agents have presented unique challenges (e.g., cytokine release syndrome [CRS]), which have required different strategies to overcome. This review provides a comprehensive overview of the clinical development of these four CD20 × CD3 bsAbs that have been investigated for the treatment of B-NHL, with a specific focus on translational assessments to select starting doses in first-in-human studies, management of CRS, application of modeling and simulation approaches to aid dose escalation and optimization/selection, and strategies used in the design of phase I-III clinical trials. By highlighting learnings and experiences from these four bsAbs assessed, which have not been summarized collectively elsewhere, we aim to promote more efficient study design for novel bsAbs in B-NHL in the future.

Lung cancer is a leading cause of cancer deaths worldwide and new therapeutic approaches are needed. This study investigates the efficacy of a new zinc oxide-based nanomedicine in a mouse model of heterotopic lung cancer. C57BL/6 mouse model with Lewis lung carcinoma (LL2) cells was used. The mice were treated with different doses of nanodrug, cisplatin, or phosphate-buffered saline. Tumor growth, metastasis, markers for oxidative stress, and immune responses, in particular the infiltration of CD8+ T cells, were examined. The nanodrug significantly reduced tumor size, inhibited metastasis, and improved survival compared to the control group. Moreover, no significant toxic effect was observed in hematological, biochemical and histopathological analyses. Furthermore, the nanodrug altered the tumor microenvironment in favor of immune system activation by modulating the level of oxidative stress and increasing CD8+ cell infiltration. The results show that this new nanomedicine may be a candidate for an effective treatment for lung cancer.

Alleviating psychological distress in women with breast cancer undergoing treatment is a major worldwide issue. The growing use of new technologies in healthcare to support patients requires a more in-depth appraisal of the optimal methods for delivering these interventions. The present study aims to explore the clinical potential of a 360° video of local landscapes to reduce psychological distress of breast cancer patients receiving intravenous chemotherapy. We presented the same content in two different viewing conditions (immersive vs. non-immersive) in order to isolate the specific effect of immersive technology.

Cyanine dyes usually serve as good fluorescence probes but not as efficient photosensitizers owing to the spin-forbidden intersystem crossing process and short excited-state lifetime. Nevertheless, the structure-derived energy release from the excited state could enable dyes to function efficiently. In this work, we developed cyanine dimers (2o-Cy, 2m-Cy, and 2p-Cy) based on exciton coupling effects by connecting two Cy5.5 molecules at the N-indole site with nonconjugated ortho/meta/para-bis(bromomethyl)benzene linkers. These dimers exhibited significantly enhanced molar extinction coefficients (32-45 × 104 M cm-1) as well as satisfactory triplet excited-state quantum yields (32-44%) and lifetimes (10.6-11.9 μs), leading to a substantially enhanced reactive oxygen species production along with efficient antitumor activity under both normoxic and hypoxic conditions. Furthermore, 2p-Cy NPs ablated primary tumors, inhibited distant tumor growth, and prevented metastatic regrowth via photoinduced innate immune activation. This dimer-based strategy represents a powerful approach to develop high-performance photosensitive dyes for antitumor photodynamic immunotherapy.

Ovarian cancer (OC) is associated with poor prognosis and immune evasion through PD-L1 expression. While anti-PD-L1 therapies have shown limited efficacy, combination strategies may enhance therapeutic outcomes. This study explores the potential of metformin to modulate the immune microenvironment and improve the efficacy of PD-L1 inhibitors in OC. An immunocompetent C57BL/6 mouse model of OC was used to evaluate the effects of metformin and PD-L1 inhibitors on tumor progression, immune cell infiltration, and cytokine expression. Mice received daily metformin treatment for 2 weeks, with PD-L1 inhibitors administered twice weekly. Tumor growth was monitored via volume measurements, immune cell infiltration was assessed by flow cytometry, and cytokine levels (Granzyme B, IFN-γ) were quantified using ELISA. Metformin significantly reduced tumor growth, increased CD8+ T cell infiltration, upregulated RBMS3, and elevated Granzyme B and IFN-γ expression. Additionally, metformin downregulated PD-L1 expression, and its combination with PD-L1 inhibitors further enhanced CD8+ T cell activity. Silencing RBMS3 reversed these effects, underscoring its critical role in immune modulation. These findings suggest that metformin, in combination with PD-L1 inhibitors, may enhance antitumor immune responses and improve treatment outcomes in OC. Targeting RBMS3 could represent a novel therapeutic approach for overcoming immune evasion in OC.

Near infrared (NIR) aggregation-induced emission (AIE)-based luminogens are emerging as powerful materials with significant potential in cancer diagnosis, imaging, and therapy applications. Of precise note are the rapidly progressing areas in the field encompassing deep-tissue imaging, resistance to photobleaching, and biomedicine. Unlike traditional aggregation-caused quenching (ACQ) fluorophores, AIE materials with NIR emissive features can revolutionize the broad transdisciplinary areas of biomedicine, therapy, and healing, making them highly effective for real-time monitoring and healthcare purposes. In this study, we have synthesized a (E)-2-(2-(4'-(2,2-diphenylvinyl)-[1,1'-biphenyl]-4-yl)vinyl)-1,3,3-trimethyl-3H-indol-1-ium, named as 3T, and explored its antiproliferative potential on MCF-7 and MDA-MB-231 breast cancer cells. The 3T molecule exhibited strong near-infrared (NIR) emission ranging from 600 to 800 nm in a 99% water fraction (fw). In silico target prediction and molecular docking identified potential target proteins and assessed their binding interactions and affinities. Further, in vitro studies demonstrated efficient cellular internalization and dose-dependent reduction in cell viability. The IC50 values of 32.26 and 35.75 μM were observed in MCF-7 and MDA-MB-231 cells, respectively. The treatment of 3T generated 2.1- and 1.9-fold increases in reactive oxygen species (ROS) for MCF-7 and MDA-MB-231 cells, respectively, and induced a change in mitochondrial membrane potential, leading to apoptosis, as confirmed by flow cytometry studies. The treatment was also effective for tumor spheroids. Thus, NIR AIEgen 3T offered several distinct advantages such as strong antiproliferative ability, stability, and imaging, positioning it as a potential candidate for cancer therapeutic applications.

Small-molecule targeting of ribonucleic acid (RNA) is a new and promising therapeutic approach, but it requires the discovery of small compounds that can specifically target particular RNA structures. In this context, a comprehensive description of the photophysical interaction features of phenothiazinium dyes such as thionine (TH)/methylene blue (MB) with transfer ribonucleic acid (tRNA) is examined by spectrophotometric titration and molecular docking analysis. After binding with tRNA, TH/MB dyes displayed emission, and absorption characteristics were significantly changed. The observed tRNA-induced spectral alterations are attributed to energy transfer from guanine base pairs, likely resulting from an intercalative interaction mode proposed for tRNA. The negative free energy change value (ΔG = ~ - 27.5 kJ mol-1) of the TH/MB dye-tRNA systems suggests that the present binding interaction is highly favorable and spontaneous. The conformational alterations of the tRNA with both dyes were verified using circular dichroism analyses. Molecular docking test results indicated that TH/MB dye molecules bonded to the tRNA cavity in a specific pattern. The novelty of this study resides in a unique role for TH/MB dyes in tRNA dysfunction, expanding our understanding of how TH/MB dyes and their tRNA complexes were used in in vitro cytotoxic investigations of human lung cancer cells.

The cytotoxic complex [(Htom6-Me){NiII(OAc)}2](OAc) (H2tom6-Me = 2,7-bis(di(6-methylpyridine-2-yl-methyl)aminomethyl)-1,8-naphthalenediol) is supposed to bind in the aquated form [(Htom6-Me){NiII(OH2)2}2]3+ to two neighboring phosphate diesters of the DNA backbone. To further support this intended molecular mode of action, difunctional ligands in the form of the dicarboxylates succinate and glutarate are used here to mimic two neighboring phosphates of the DNA backbone. The complex [(Htom6-Me){NiII(OAc)}2](OAc) is treated with 3 equiv. HCl to protonate the acetates providing presumably [(Htom6-Me){NiII(OH2)2}2]3+, which is reacted with the dicarboxylates yielding the complexes [(Htom6-Me){NiII(μ-succ)NiII}]+ and [(Htom6-Me){NiII(μ-glut)NiII}]+ confirmed by single-crystal X-ray diffraction. The sterical constraints of the dicarboxylates enforces shorter Ni⋯Ni distances demonstrating the flexibility of the coordination compartments despite the rigid 1,8-naphthalenediol backbone. These steric constraints by the pull effect of the organic spacers affect the NiII-ligand bonds and are reflected in FTIR and UV-Vis-NIR spectroscopic but not magnetic signatures. The comparison to a related CuII complex indicates a severe impact of the 6-methyl groups of the pyridine donors on the relative orientation of the anticipated phosphate binding sites in these complexes. The consequences for a rational strengthening of the binding to DNA and hence increase of the cytotoxicity by possible ligand modifications are discussed.

In our work, we focused on the development of nanostructured lipid carriers (NLCs) loaded with dexibuprofen (DXI) and their application for cancer therapy by proposing the binding of phospholipids with this non-steroidal anti-inflammatory drug (NSAID) to obtain new delivery systems.