ABSTRACT
Chemotherapeutics can induce immunogenic cell death (ICD) in tumor cells, offering new possibilities for cancer therapy. However, the efficiency of the immune response generated is insufficient due to the inhibitory nature of the tumor microenvironment (TME). Here, we developed a pH/reactive oxygen species (ROS) dual-response system to enhance chemoimmunotherapy for melanoma. The system productively accumulated in tumors by specific binding of phenylboronic acid (PBA) to sialic acids (SA). The nanoparticles (NPs) rapidly swelled and released quercetin (QUE) and doxorubicin (DOX) upon the stimulation of tumor microenvironment (TME). The in vitro and in vivo results consistently demonstrated that the NPs improved anti-tumor efficacy and prolonged survival of mice, significantly enhancing the effects of the combination. Our study revealed DOX was an ICD inducer, stimulating immune responses and promoting maturation of dendritic cells (DCs). Additionally, QUE served as a TME regulator by inhibiting the cyclooxygenase-2 (COX2)-prostaglandin E2 (PGE2) axis, which influenced various immune cells, including increasing cytotoxic T cells (CLTs) infiltration, promoting M1 macrophage polarization, and reducing regulatory T cells (Tregs) infiltration. The combination synergistically facilitated chemoimmunotherapy efficacy by remodeling the immunosuppressive microenvironment. This work presents a promising strategy to increase anti-tumor efficiency of chemotherapeutic agents.
ABSTRACT
Osteosarcoma is usually resistant to immunotherapy and, thus primarily relies on surgical resection and high-dosage chemotherapy. Unfortunately, less invasive or toxic therapies such as photothermal therapy (PTT) and chemodynamic therapy (CDT) generally failed to show satisfactory outcomes. Adequate multimodal therapies with proper safety profiles may provide better solutions for osteosarcoma. Herein, a simple nanocomposite that synergistically combines CDT, PTT, and chemotherapy for osteosarcoma treatment was fabricated. In this composite, small 2D NiFe-LDH flakes were processed into 3D hollow nanospheres via template methods to encapsulate 5-Fluorouracil (5-FU) with high loading capacity. The nanospheres were then adsorbed onto larger 2D Ti3C2 MXene monolayers and finally shielded by bovine serum albumin (BSA) to form 5-FU@NiFe-LDH/Ti3C2/BSA nanoplatforms (5NiTiB). Both in vitro and in vivo data demonstrated that the 5-FU induced chemotherapy, NiFe-LDH driven chemodynamic effects, and MXene-based photothermal killing collectively exhibited a synergistic "all-in-one" anti-tumor effect. 5NiTiB improved tumor suppression rate from <5% by 5-FU alone to â¼80.1%. This nanotherapeutic platform achieved higher therapeutic efficacy with a lower agent dose, thereby minimizing side effects. Moreover, the composite is simple to produce, enabling the fine-tuning of dosages to suit different requirements. Thus, the platform is versatile and efficient, with potential for further development.
ABSTRACT
The viscosity of household care products plays an important role in pleasant delivery using consumer experience at home. A novel solution to mitigate the sharp rising of viscosities at low temperatures of detergents was proposed. By designing the formulation of the surfactant blend, formulators can achieve acceptable viscosity profiles in the temperature range encountered in daily life. The verification and modulation of formulas bearing parabolic viscosity-temperature behavior were systematically studied, including in single, binary, and ternary systems, based on the modulation of sodium ethoxylated alkyl sulfate (AES) by other anions, zwitterions, and nonions. The R ratio theory was used to have a better understanding of the molecular assembly of surfactants behind the parabolic behavior exhibited in rheology analyses. One of the key findings is that the parabolic viscosity-temperature phenomenon could be easily observed in the highly hydrated ethoxylated anionic systems like AES-based systems. For those anions lacking ethoxylation, especially sodium linear alkylbenzene sulfonate (LAS), the monotonic variation of hydration affinity with temperature led to the disappearance of parabola in the observed temperature window (>0 °C). Moreover, salinity played an important role in the hydration affinity of the polar group and the interaction between the hydrophilic headgroups. A balanced salinity should be optimized to modulate the hydration affinity in a desired range so that the parabola could be easily tuned within the target temperature region. These findings provide opportunities for the formulators in the household care industry to design products with better pourability through carefully selecting a combination of surfactants and fine-tuning their ratios to improve consumer use experience, especially in winter.
ABSTRACT
Long and automatic control of blood glucose levels in diabetic patients could solve the problems caused by frequent insulin injections. Herein, we exploited the protection potential of erythrocytes by a "hitchhiking" strategy to significantly prolong the blood circulation time of a specifically-designed smart hitchhiking insulin delivery system (SHIDS). In the SHIDS, insulin, glucose oxidase, and catalase were co-loaded into nanoparticles formed by modified chitosan. The free glucosamines in chitosan anchor glucose transporters on the surface of erythrocytes, allowing erythrocyte-hitchhiking in the blood flow. A high glucose level triggers quick insulin release from the SHIDS to reduce the glucose level, which then slows the insulin release. This closed-loop glucose regulation by the SHIDS effectively controlled blood glucose within the normal range for at least 24 h and under 250 mg dL-1 for â¼48 h with one injection. This injectable erythrocyte-hitchhiking nanoplatform, which achieves long-term and automatic blood glucose control, thus has potential for further development. As the carrier could be used for delivering other drugs/agents or interacting with other substances, the hitchhiking strategy is versatile and may be applied in other medical applications too.