Injectable composite hydrogels embedded with gallium-based liquid metal particles for solid breast cancer treatment via chemo-photothermal combination.

Photothermal therapy (PTT) holds great promise as a cancer treatment modality by generating localized heat at the tumor site. Among various photothermal agents, gallium-based liquid metal (LM) has been widely used as a new photothermal-inducible metallic compound due to its structural transformability. To overcome limitations of random aggregation and dissipation of administrated LM particles into a human body, we developed LM-containing injectable composite hydrogel platforms capable of achieving spatiotemporal PTT and chemotherapy. Eutectic gallium-indium LM particles were first stabilized with 1,2-Distearoyl-sn­glycero-3-phosphoethanolamine (DSPE) lipids. They were then incorporated into an interpenetrating hydrogel network composed of thiolated gelatin conjugated with 6-mercaptopurine (MP) chemodrug and poly(ethylene glycol)-diacrylate. The resulted composite hydrogel exhibited sufficient capability to induce MDA-MB-231 breast cancer cell death through a multi-step mechanism: (1) hyperthermic cancer cell death due to temperature elevation by near-infrared laser irradiation via LM particles, (2) leakage of glutathione (GSH) and cleavage of disulfide bonds due to destruction of cancer cells. As a consequence, additional chemotherapy was facilitated by GSH, leading to accelerated release of MP within the tumor microenvironment. The effectiveness of our composite hydrogel system was evaluated both in vitro and in vivo, demonstrating significant tumor suppression and killing. These results demonstrate the potential of this injectable composite hydrogel for spatiotemporal cancer treatment. In conclusion, integration of PTT and chemotherapy within our hydrogel platform offers enhanced therapeutic efficacy, suggesting promising prospects for future clinical applications. STATEMENT OF SIGNIFICANCE: Our research pioneers a breakthrough in cancer treatments by developing an injectable hydrogel platform incorporating liquid metal (LM) particle-mediated photothermal therapy and 6-mercaptopurine (MP)-based chemotherapy. The combination of gallium-based LM and MP achieves synergistic anticancer effects, and our injectable composite hydrogel acts as a localized reservoir for specific delivery of both therapeutic agents. This platform induces a multi-step anticancer mechanism, combining NIR-mediated hyperthermic tumor death and drug release triggered by released glutathione from damaged cancer populations. The synergistic efficacy validated in vitro and in vivo studies highlights significant tumor suppression. This injectable composite hydrogel with synergistic therapeutic efficacy holds immense promise for biomaterial-mediated spatiotemporal treatment of solid tumors, offering a potent targeted therapy for triple negative breast cancers.

Dielectrophoretic Capture of Cancer-Derived Small-Extracellular-Vesicle-Bound Janus Nanoparticles via Lectin-Glycan Interaction.

Glycosylation is closely related to cellular metabolism and disease progression. In particular, glycan levels in cancer cells and tissues increase during cancer progression. This upregulation of glycosylation in cancer cells may provide a basis for the development of new biomarkers for the targeting and diagnosis of specific cancers. Here, they developed a detection technology for pancreatic cancer cell-derived small extracellular vesicles (PC-sEVs) based on lectin-glycan interactions. Lectins specific for sialic acids are conjugated to Janus nanoparticles to induce interactions with PC-sEVs in a dielectrophoretic (DEP) system. PC-sEVs are selectively bound to the lectin-conjugated Janus nanoparticles (lectin-JNPs) with an affinity comparable to that of conventionally used carbohydrate antigen 19-9 (CA19-9) antibodies. Furthermore, sEVs-bound Lectin-JNPs (sEVs-Lec-JNPs) are manipulated between two electrodes to which an AC signal is applied for DEP capture. In addition, the proposed DEP system can be used to trap the sEVs-Lec-JNP on the electrodes. Their results, which are confirmed by lectin-JNPs using the proposed DEP system followed by target gene analysis, provide a basis for the development of a new early diagnostic marker based on the glycan characteristics of PC-sEVs. In turn, these novel detection methods could overcome the shortcomings of commercially available pancreatic cancer detection techniques.

Liquid-Metal Core-Shell Particles Coated with Folate and Phospholipids for Targeted Drug Delivery and Photothermal Treatment of Cancer Cells.

Recently, several methods have been used for cancer treatment. Among them, chemotherapy is generally used, but general anticancer drugs may affect normal cells and tissues, causing various side effects. To reduce the side effects and increase the efficacy of anticancer drugs, a folate-based liquid-metal drug nanodelivery system was used to target the folate receptor, which is highly expressed in cancer cells. A phospholipid-based surface coating was formed on the surface of liquid-metal nanoparticles to increase their stability, and doxorubicin was loaded as a drug delivery system. Folate on the lipid shell surface increased the efficiency of targeting cancer cells. The photothermal properties of liquid metal were confirmed by near-infrared (NIR) laser irradiation. After treating cancerous and normal cells with liquid-metal particles and NIR irradiation, the particles were specifically bound to cancer cells for drug uptake, confirming photothermal therapy as a drug delivery system that is expected to induce cancer cell death through comprehensive effects such as vascular embolization in addition to targeting cancer cells.

Comparison of the incidence rates of hip and vertebral fragility fractures according to cataract surgery in elderly population: a nationwide cohort study.

Elderly patients who underwent cataract surgery showed lower prevalence and cumulative incidence rates of hip and vertebral fragility fractures than those who did not. Therefore, cataract surgery in elderly patients may reduce the incidence of hip and vertebral fragility fractures. PURPOSE: The purpose of this study was to compare the incidence rates of hip and vertebral fragility fractures between patients who underwent cataract surgery and those who did not, and to investigate the effect of cataract surgery on the incidence of fragility fracture in elderly population using nationwide claims data. METHODS: A total of 558,147 participants from the National Health Insurance Service - Senior cohort were included. The participants were set into the hip fracture group (507,651) and vertebral fracture group (507,899) depending on the type of fracture. RESULTS: The number of hip fractures that occurred in the non-cataract surgery (NC) group was 36,971 (9.9%), while 8850 (6.6%) hip fractures occurred in the cataract surgery (C) group. The number of vertebral fractures that occurred in the NC group was 38,689 (10.3%), while 10,112 (7.6%) vertebral fractures occurred in the C group (all p < .001). The hazard ratios of hip and vertebral fractures were 0.58 and 0.60 for the total population that had undergone cataract surgery (all p < .001). The cumulative incidence rates of both fractures in the cataract surgery group were significantly lower than those in the non-cataract surgery group during 10 years (all p < .0001). CONCLUSION: Elderly patients who underwent cataract surgery showed a lower prevalence of hip and vertebral fragility fractures than those who did not. In addition, the cumulative incidence rates of both fractures in the cataract surgery group were lower than those in the non-cataract surgery group. Therefore, cataract surgery in elderly patients may reduce the incidence of hip and vertebral fragility fractures.

Exosome-mediated diagnosis of pancreatic cancer using lectin-conjugated nanoparticles bound to selective glycans.

The unique profile of upregulated glycosylation in metastatic cancer cells may form the basis for the development of new biomarkers for the targeting and diagnosis of specific cancers. This study introduces a pancreatic cancer cell-derived exosome detection technology, which is based on the specific binding of lectins to distinctive glycan profiles on the surface of exosomes. Lectins with a high and specific affinity for sialic acid or fucose were attached to bifunctional Janus nanoparticles (JNPs), which facilitated interactions with pancreatic cancer cell-derived exosomes in a microfluidic device. Here, we show that pancreatic cancer cell-derived exosomes from two cell lines and plasma samples collected from patients diagnosed with pancreatic cancer were successfully captured on the lectin-conjugated JNPs with affinities that were comparable to those of CA19-9, a conventional antibody. In addition, exosome detection using our platform could differentiate between metastatic and nonmetastatic pancreatic cancer cells. This study opens the possibility to achieve a new early diagnosis marker based on the glycan properties of pancreatic cancer cell-derived exosomes.

Chemoresistance of Cancer Cells: Requirements of Tumor Microenvironment-mimicking In Vitro Models in Anti-Cancer Drug Development.

For decades, scientists have been using two-dimensional cell culture platforms for high-throughput drug screening of anticancer drugs. Growing evidence indicates that the results of anti-cancer drug screening vary with the cell culture microenvironment, and this variation has been proposed as a reason for the high failure rate of clinical trials. Since the culture condition-dependent drug sensitivity of anti-cancer drugs may negatively impact the identification of clinically effective drug candidates, more reliable in vitro cancer platforms are urgently needed. In this review article, we provide an overview of how cell culture conditions can alter drug efficacy and highlight the importance of developing more reliable cancer drug testing platforms for use in the drug discovery process. The environmental factors that can alter drug delivery and efficacy are reviewed. Based on these observations of chemoresistant tumor physiology, we summarize the recent advances in the fabrication of in vitro cancer models and the model-dependent cytotoxicity of anti-cancer drugs, with a particular focus on engineered environmental factors in these platforms. It is believed that more physiologically relevant cancer models can revolutionize the drug discovery process.

Oxygen-Carrying Micro/Nanobubbles: Composition, Synthesis Techniques and Potential Prospects in Photo-Triggered Theranostics.

Microbubbles and nanobubbles (MNBs) can be prepared using various shells, such as phospholipids, polymers, proteins, and surfactants. MNBs contain gas cores due to which they are echogenic and can be used as contrast agents for ultrasonic and photoacoustic imaging. These bubbles can be engineered in various sizes as vehicles for gas and drug delivery applications with novel properties and flexible structures. Hypoxic areas in tumors develop owing to an imbalance of oxygen supply and demand. In tumors, hypoxic regions have shown more resistance to chemotherapy, radiotherapy, and photodynamic therapies. The efficacy of photodynamic therapy depends on the effective accumulation of photosensitizer drug in tumors and the availability of oxygen in the tumor to generate reactive oxygen species. MNBs have been shown to reverse hypoxic conditions, degradation of hypoxia inducible factor 1α protein, and increase tissue oxygen levels. This review summarizes the synthesis methods and shell compositions of micro/nanobubbles and methods deployed for oxygen delivery. Methods of functionalization of MNBs, their ability to deliver oxygen and drugs, incorporation of photosensitizers and potential application of photo-triggered theranostics, have also been discussed.