In cancer treatment, it is critical to enhance drug delivery efficiency to the target area while minimizing the side effects of chemotherapeutic drugs. Although intravenous administration of anticancer agents is commonly used, it often results in blood vessel damage and systemic side effects as well as poor targeted delivery. Therefore, developing new drug delivery formulations is essential to improve anticancer efficacy while reducing side effects. Herein, a nanohybrid methodology is presented to improve the targeted delivery of doxorubicin (DOX) for treating hepatocellular carcinoma (HCC) and to minimize vascular damage. An albumin-glucosamine (AG) lipid complex (LC), composed of stearyl glycyrrhetinate (SG) and DSPE-PEG, is designed to serve as a liver cancer-specific delivery system. The nanohybrid formulation, SGLC/DOX@AG, demonstrates significant anticancer activity and reduced side effects, as demonstrated by in vitro, in vivo, and cancer-on-a-chip models. This study presents a novel carrier design and application model for drug formulation development and efficacy validation, providing insights into therapeutic development for HCC.

A radiopaque hydrogel-in-liposome (RHL) system was developed for micro-computed tomography (μCT) imaging of tumor tissue and simultaneous delivery of a cytotoxic agent. Iopamidol (IPD) and doxorubicin (DOX) were incorporated as the CT contrast and anti-cancer agents, respectively. The presence of a polyethylene glycol hydrogel core in the liposomes was confirmed via attenuated total reflectance Fourier transform infrared, proton nuclear magnetic resonance, and selective solvent extraction. Nano-sized (∼160 nm) spherical DOX/IPD-loaded RHLs with a narrow size distribution and negative zeta potential were successfully fabricated. The RHLs demonstrated enhanced cellular uptake of DOX in SCCVII cells compared to conventional radiopaque liposomes, likely due to clathrin-mediated endocytosis. Additionally, pH-dependent DOX release and reduced IPD leakage were observed. In vivo studies using SCCVII tumor-xenografted mice showed that RHLs exhibited improved CT contrast efficiency and anti-tumor efficacy, along with systemic biocompatibility, attributed to enhanced tumor-targeting properties. These findings suggest that the RHL system could serve as a promising nano-platform for tumor theranostics.

Aggregation-induced emission (AIE) theranostics has received considerable attention because of its potential applications in bioimaging and photodynamic therapy (PDT). Herein, we report a series of phthalimide-based AIEgens that are selectively localized in lipid droplets (LDs) in cancer cells and simultaneously generate reactive oxygen species (ROS) under light irradiation. The enhanced photostability resulting from the AIE properties of LPSP2 enabled the long-term tracking of LDs during ferroptotic cell death triggered by LPSP2 under PDT conditions. As the irradiation time increased, the lipid peroxides generated by LPSP2 were transported from the LDs to the endoplasmic reticulum (ER), where oxidative stress activates NLRP3, leading to pyroptotic cell death. The spatiotemporal control of lipid peroxidation achieved by LPSP2 revealed sequential activation of ferroptosis followed by pyroptosis, depending on the irradiation duration. Our research demonstrates novel LD-targeted theranostics with unprecedented induction of ferroptotic and pyroptotic cell death under PDT, which will enrich our understanding of cancer cell death mechanisms toward a more efficient therapeutic strategy.

In cancer treatment, it is critical to enhance drug delivery efficiency to the target area while minimizing the side effects of chemotherapeutic drugs. Although intravenous administration of anticancer agents is commonly used, it often results in blood vessel damage and systemic side effects as well as poor targeted delivery. Therefore, developing new drug delivery formulations is essential to improve anticancer efficacy while reducing side effects. Herein, a nanohybrid methodology is presented to improve the targeted delivery of doxorubicin (DOX) for treating hepatocellular carcinoma (HCC) and to minimize vascular damage. An albumin-glucosamine (AG) lipid complex (LC), composed of stearyl glycyrrhetinate (SG) and DSPE-PEG, is designed to serve as a liver cancer-specific delivery system. The nanohybrid formulation, SGLC/DOX@AG, demonstrates significant anticancer activity and reduced side effects, as demonstrated by in vitro, in vivo, and cancer-on-a-chip models. This study presents a novel carrier design and application model for drug formulation development and efficacy validation, providing insights into therapeutic development for HCC.

A radiopaque hydrogel-in-liposome (RHL) system was developed for micro-computed tomography (μCT) imaging of tumor tissue and simultaneous delivery of a cytotoxic agent. Iopamidol (IPD) and doxorubicin (DOX) were incorporated as the CT contrast and anti-cancer agents, respectively. The presence of a polyethylene glycol hydrogel core in the liposomes was confirmed via attenuated total reflectance Fourier transform infrared, proton nuclear magnetic resonance, and selective solvent extraction. Nano-sized (∼160 nm) spherical DOX/IPD-loaded RHLs with a narrow size distribution and negative zeta potential were successfully fabricated. The RHLs demonstrated enhanced cellular uptake of DOX in SCCVII cells compared to conventional radiopaque liposomes, likely due to clathrin-mediated endocytosis. Additionally, pH-dependent DOX release and reduced IPD leakage were observed. In vivo studies using SCCVII tumor-xenografted mice showed that RHLs exhibited improved CT contrast efficiency and anti-tumor efficacy, along with systemic biocompatibility, attributed to enhanced tumor-targeting properties. These findings suggest that the RHL system could serve as a promising nano-platform for tumor theranostics.

Aggregation-induced emission (AIE) theranostics has received considerable attention because of its potential applications in bioimaging and photodynamic therapy (PDT). Herein, we report a series of phthalimide-based AIEgens that are selectively localized in lipid droplets (LDs) in cancer cells and simultaneously generate reactive oxygen species (ROS) under light irradiation. The enhanced photostability resulting from the AIE properties of LPSP2 enabled the long-term tracking of LDs during ferroptotic cell death triggered by LPSP2 under PDT conditions. As the irradiation time increased, the lipid peroxides generated by LPSP2 were transported from the LDs to the endoplasmic reticulum (ER), where oxidative stress activates NLRP3, leading to pyroptotic cell death. The spatiotemporal control of lipid peroxidation achieved by LPSP2 revealed sequential activation of ferroptosis followed by pyroptosis, depending on the irradiation duration. Our research demonstrates novel LD-targeted theranostics with unprecedented induction of ferroptotic and pyroptotic cell death under PDT, which will enrich our understanding of cancer cell death mechanisms toward a more efficient therapeutic strategy.

, suggesting that PLCSA-AD could be promising nanotherapeutics for bone tumor treatment.

Photodynamic therapy (PDT) is often hindered by poor tumor selectivity and inefficient drug delivery. Herein, a lipid-hybridized phototherapeutic nanoplatform, LBCIN, is presented to overcome these barriers by integrating a reactive oxygen species (ROS)-triggered molecular logic gate with a synergistic dual-light strategy. The molecular core consists of BdTT-BNBE, a novel photosensitizer prodrug designed for tumor microenvironment-selective activation. Upon triggering by endogenous ROS, BdTT-BNBE undergoes cleavage to release the active photosensitizer and a para-quinone methide (pQM) intermediate. This mechanism creates a dual-action cascade: generating a potent ROS offense while simultaneously scavenging glutathione (GSH) via pQM, thereby systematically dismantling the tumor's antioxidant defense. For stable delivery, the payload is encapsulated within a chondroitin sulfate-based core with a lipid corona, offering superior colloidal stability and CD44-mediated targeting. Furthermore, a unique dual-light sequence is employed to maximize efficacy. Initial 808 nm laser irradiation activates the carrier-conjugated indocyanine green derivative (psICG), providing a "photothermal priming" effect that enhances membrane permeability and nanoparticle uptake. This facilitates subsequent white light-emitting diode (LED) irradiation, triggering a potent PDT effect amplified by intermolecular energy transfer and ferroptosis induction. This engineered integration of ROS-responsive chemistry and sequential light activation results in durable tumor eradication with a high safety profile.

Acute lung injury (ALI) is characterized by severe inflammation in lung tissue, excessive immune response and impaired lung function. In hospitalized high-risk patients and cases of secondary infection due to surgical contamination, it can lead to higher mortality rates and require immediate intervention. Currently, clinical treatments are limited in symptomatic therapy as mechanical ventilation and corticosteroids, having insufficient efficacy in mitigating the cause of progression to severe illness. Here we report a pulmonary targeting lung-homing nanoliposome (LHN) designed to attenuate excessive Neutrophil Extracellular Trap formation (NETosis) through sivelestat and DNase-1, coupled with an anti-inflammatory effect mediated by 25-hydroxycholesterol (25-HC), offering a promising intervention for the acute phase of ALI. Through intratracheal delivery, we intend prompt and constant action within the lungs to effectively prevent excessive NETosis. Isolated neutrophils from blood samples of severe ARDS patients demonstrated significant anti-NETosis effects, as well as reduced proinflammatory cytokine secretion. Furthermore, in a murine model of LPS-induced ALI, we confirmed improvements in lung histopathology, and early respiratory function. Also, attenuation of systemic inflammatory response syndrome (SIRS), with notable reductions in NETosis and neutrophil trafficking was investigated. This presents a targeted therapeutic approach that can be applied in early stages of high-risk patients to prevent severe pulmonary disease progression.

Abstract Background Uricase-based enzyme replacement therapies have emerged as an effective treatment for refractory gout and tumor lysis syndrome. However, their clinical adoption has been hindered by challenges such as instability, rapid clearance, and immune responses. While formulations such as PEGylated uricase have demonstrated clinical efficacy, they are limited by the development of anti-PEG antibodies, which reduces their therapeutic effectiveness. Thus, innovative drug delivery strategies are required to address these limitations and increase the effectiveness of uricase therapies. Area covered This review provides a comprehensive overview of uricase as a therapeutic enzyme and discusses both the approved formulations and recent advances in drug delivery systems (DDS) aimed at overcoming key challenges. It focuses on nanoparticle-based and polymer-conjugated systems designed to improve stability, extend enzyme half-life, and reduce immunogenicity. Additionally, this review explores the use of lipid-based carriers, polymeric nanoparticles, and inorganic frameworks to optimize enzyme delivery, offering insights into their potential to increase pharmacokinetics and minimize immune responses. Expert opinion Although uricase-based therapies show considerable promise for refractory gout and tumor lysis syndrome, challenges related to their stability, pharmacokinetics, and immunogenicity persist. Advanced DDS strategies offer viable solutions by stabilizing enzymes, prolonging circulation, and mitigating immune reactions. Achieving therapeutic efficacy requires balancing immune evasion and enzymatic activity to ensure long-term effectiveness. Further innovations in DDS are essential to develop safer and more reliable uricase therapies, expand their clinical use, and address unmet patient needs.