pH-responsive Release Research Articles

Sustained therapeutic effects of self-assembled hyaluronic acid nanoparticles loaded with α-Ketoglutarate in various osteoarthritis stages

Osteoarthritis (OA) is a prevalent degenerative disease characterized by irreversible destruction of articular cartilage, for which no current drugs are known to modify its progression. While intra-articular (IA) injections of hyaluronic acid (HA) offer temporary relief, their effectiveness and long-term benefits are debated. Alpha-ketoglutarate (αKG) has potential chondroprotective properties, but its use is limited by a short half-life and poor cartilage-targeting efficiency. Here, we developed self-assembled HA-αKG nanoparticles (NPs) to combine the benefits of both HA and αKG, showing stability, bioavailability, and sustained pH-responsive release in the knee joint. In both early and advanced OA stages in mice, HA, αKG, and HA-αKG NPs could relieve pain, enhance mobility, and reduce cartilage damage, with HA-αKG NPs demonstrating the best efficacy. Mechanistically, αKG not only promotes cartilage matrix synthesis but also inhibits degradation by activating the PERK-ATF4 signaling pathway to reduce endoplasmic reticulum stress (ERS) in chondrocytes. This study highlights the therapeutic potential of HA-αKG NPs for treating various OA stages, with efficient and sustained effects, suggesting rapid clinical adoption and high acceptability among clinicians and patients.

Antimicrobial Peptide Hydrogel with pH-Responsive and Controllable Drug Release Properties for the Efficient Treatment of Helicobacter pylori Infection.

Helicobacter pylori is the primary cause of gastric adenocarcinoma, which afflicts more than half of the world's population and seriously affects human health. However, achieving efficient treatment of H. pylori infection by effective drug delivery and bioavailability after oral administration remains a challenge due to the harsh microenvironment, short drug retention time, and physiological barriers in the stomach. Moreover, H. pylori has shown resistance to many clinical antibiotics. Antimicrobial peptides (AMPs) exhibit substantial therapeutic efficacy against H. pylori, while they are not likely to induce drug resistance, suggesting their potential utility for the treatment of diseases related to H. pylori. In this paper, we report the design and synthesis of an AMP (GE33) hydrogel with pH-responsive and controlled peptide release properties, in which the minimal inhibitory concentration of the AMP against H. pylori is as low as 1 μg/mL. GE33 self-assembles into a stable peptide hydrogel under neutral pH conditions but decomposes into monomers or oligomers under acidic conditions. Upon oral administration of the hydrogel, the acidic gastric environment would facilitate rapid release of active AMP molecules from the hydrogel and immediate targeting of H. pylori in the stomach wall. Additionally, the remaining peptide is protected in the hydrogel, extending its retention time in the stomach, so that persistent drug release is achieved. The controlled and sustained release manner of the active molecule GE33, which enhances drug bioavailability, along with its excellent bactericidal efficacy opens a great potential for treating H. pylori infection.

Injectable Salecan/hyaluronic acid-based hydrogels with antibacterial, rapid self-healing, pH-responsive and controllable drug release capability for infected wound repair

Designing materials for wound dressings with superior therapeutic benefits, self-healing and injectable characteristics is important in clinical practice. Herein, a new self-healing injectable hydrogel was prepared via thermal treatment and dynamic Schiff base reaction by mixing oxidized hyaluronic acid (OHA) and hydrazided Salecan (Sal-ADH). The versatility of the wound dressing was confirmed by studying the inherent rheological properties, high swelling rate, sustained-release behavior of the drug, pH/hyaluronidase-dependent biodegradation, in vitro antimicrobial as well as in vivo wound healing performance. The presence of the antimicrobial drug polyhexamethylene biguanide (PHMB) conferred good antimicrobial properties to the Sal-ADH/OHA/PHMB (SOP) hydrogel, which could effectively prevent wound infection (the width of the inhibition circle of SOP-0.20 hydrogel was 4.97 mm, 5.93 mm for Staphylococcus aureus and Escherichia coli, respectively). The findings suggested that SOP hydrogel exhibited remarkable self-healing and injectability properties, as well as excellent hemostasis and biocompatibility. In vivo experiments indicated that the application of SOP hydrogels would obviously accelerate wound healing and attenuate the inflammatory response while increasing collagen deposition and angiogenesis. Altogether, antibacterial SOP hydrogels with moderate mechanical properties, pH-responsive release, excellent injectability, exceptional self-healing ability and anti-inflammatory effects could expand potential applications of injectable hydrogels in the biomedical field.

Nanosheet-assembled porous-wall hollow hydroxyapatite microspheres prepared by a template-free hydrothermal method for pH-responsive drug release

Template residues during the preparation of hydroxyapatite (HA) microspheres with hollow structures limit their biological applications to some extent. In this study, the nanosheet-assembled porous-wall hollow HA microspheres were successfully synthesized by a template-free hydrothermal method. SEM and TEM observations revealed that the prepared hollow HA microspheres were about 3–7 μm in diameter and were composed of an interior cavity and a porous shell assembled by nanosheets (consisting of radial nanorods arranged side-by-side). A possible mechanism for the formation of the hollow HA microspheres was proposed based on the time-gradient experiments. Furthermore, the hollow HA microspheres exhibited excellent vancomycin loading capacity (101.3 mg/g) and pH-responsive release properties. This study provides new inspiration for the design and various applications of hollow materials.

Eco-friendly, pH-sensitive curcumin-loaded sodium alginate/hydroxyapatite/quaternary ammonium chitosan microspheres with enhanced antibacterial and antioxidant activities for fruit preservation

The development of intelligent responsive reactive packaging materials with natural polymers shows excellent potential in food preservation. In this study, eco-friendly, pH-sensitive sodium alginate (SA)/hydroxyapatite (HA)/quaternary ammonium chitosan (HACC) composite microspheres loading curcumin (CUR) with excellent antibacterial and antioxidant activities were successfully synthesized. Scanning electron microscopy (SEM) and nitrogen adsorption/desorption tests indicated that the doping of HA substantially increased the specific surface area and pore volume of the microspheres. The loading experiments showed that the efficiency of the microspheres was significantly increased by 49.47 % and 55.10 %, respectively, when HA and HACC were incorporated into the SA network. The release test results suggested that the release rate of SA/HA/HACC microspheres loading CUR (SA/HA/HACC@CUR) increased as the pH decreased, demonstrating notable pH-responsive release characteristics. DPPH free radical scavenging experiments demonstrated that the SA/HA/HACC@CUR had excellent and long-lasting antioxidant capacity. The antibacterial experiments revealed that the SA/HA/HACC@CUR had excellent antibacterial properties, with inhibition rates of 88.73 % and 92.52 % against E. coli and S. aureus, respectively. Making coatings out of microspheres could effectively slow down the rotting and deterioration of cherry tomatoes during storage, suggesting that microspheres with intelligent responses have a broad application prospect in fruit preservation.

Curcumin/nido-carborane complexes incorporated with crown ether/sodium alginate encapsulated drug delivery strategies exhibit pH-responsive release and enhanced in vitro anti-tumor activity

Curcumin has excellent anti-tumor activity, but its instability at physiological pH, low bioavailability and poor targeting limit curcumin to further become an excellent anticancer drug. In this study, two curcumin/nido-carborane fluorescent polymers, curcumin-borane-crown ether coated by sodium alginate (SA-CBC) and curcumin-borane-crown ether (CBC), were prepared, and SA-CBC with better properties to be the most promising anti-tumor drugs. Crown ether/sodium alginate drug delivery strategies can improve the release property of curcumin. Nido-carborane enhances the targeting of curcumin and the inhibiting effect on tumor cells. After testing, the fluorescence lifetime of SA-CBC was 4.72 ns, indicating good fluorescence properties. In vitro drug release results showed that the constructed drug delivery system released curcumin at a controlled rate. The results of transmission electron microscopy and particle size showed that SA-CBC was well encapsulated, with a particle size of less than 200 nm, easy to be absorbed in vivo. Bioactivity studies showed that SA-CBC had a strong affinity and inhibiting effect on tumor cells, and the inhibition rate could reach 84.5 %. In conclusion, this study provides an innovative protocol for the design of curcumin anticancer drugs and lays the foundation for the development of more effective anti-tumor drugs with small side effects.

The efficacy and safety of pH-responsive and photothermal-sensitive multifunctional nanoparticles loaded with cryptotanshinone for the treatment of gastric cancer.

A multifunctional polydopamine/mesoporous silica nanoparticles loaded cryptotanshinone (PDA/MSN@CTS) was synthesized and subjected to investigating its physicochemical properties and anti-gastric cancer (GC) effects. Utilizing network pharmacology and molecular docking techniques, CTS was identified as our final research target. The structural morphology and physicochemical properties of PDA/MSN@CTS were examined. Near-infrared (NIR) laser was employed to evaluate the photothermal properties of the PDA/MSN@CTS, along with pH-responsive and NIR-triggered release assessments. In vitro experiments evaluated the impact of PDA/MSN@CTS on the malignant behavior of AGS gastric cells. A subcutaneous tumor model was further established to evaluate the in vivo safety of PDA/MSN@CTS. Furthermore, the in vivo photothermal efficacy of PDA/MSN@CTS, in addition to its combined effect with photothermal therapy (PTT), was investigated. Uniform and stable PDA/MSN@CTS had been successfully synthesized and demonstrated efficient release under tumor environment and NIR irradiation. Upon increasing NIR laser conditions, in vivo cytotoxicity, apoptosis rate, reactive oxygen species scavenging ability, and suppression of migration and invasion of AGS cells by PDA/MSN@CTS were significantly enhanced. In vivo assessments revealed excellent blood compatibility and biosafety of PDA/MSN@CTS, alongside robust tumor tissue targeting. Combining nanoparticles with PTT facilitated the anti-GC effects of PDA/MSN@CTS. Compared to free drugs, PDA/MSN@CTS exhibits higher selectivity towards cancer cells, demonstrating effective anticancer activity and biocompatibility both in vitro and in vivo. Furthermore, our nanomaterial possesses excellent photothermal properties, and under NIR conditions, PDA/MSN@CTS exhibits synergistic therapeutic effects.

Hydroxychloroquine loaded hollow apoferritin nanocages for cancer drug repurposing and autophagy inhibition

Hydroxychloroquine sulfate (HCQ) is currently being repurposed for cancer treatment. The antitumor mechanism of HCQ is inhibition of cellular autophagy, but its therapeutic potential is severely limited by poor solubility, lack of tumor targeting and lower cellular uptake. Therefore, utilization of human H-chain apoferritin (HFn) composed only of heavy subunits is an attractive approach for tumor targeting drug delivery. This study focused on pH-triggered encapsulation of HCQ within the inner cavity of HFn to form HFn@HCQ nanoparticles for tumor-targeted drug delivery. Characterization using a range of techniques has been used to confirm the successful establishment of HFn@HCQ. HFn@HCQ exhibited pH-responsive release behavior, with almost no drug release at pH 7.4, but 80% release at pH 5.0. Owing to its intrinsic binding to transferrin receptor 1 (TfR1), HFn@HCQ was significantly internalized through TfR1-mediated endocytosis, with a 4.4-fold difference of internalization amount across cell lines. Additionally, HFn@HCQ enhanced the antitumor effect against four different cancer cell lines when compared against HCQ alone, especially in TfR1 high-expressing cells, where the inhibitory effect was 3-fold higher than free HCQ. The autophagy inhibition of HFn@HCQ has been demonstrated, which is a major pathway to induce cancer cell death. According to current findings, HFn based drug delivery is a promising strategy to target and kill TfR1 overexpressing tumor cells.

Graphene Oxide-Based Antifungal Pesticide Delivery System for Tobacco Fungal Disease (Tobacco Target Spot) Control.

In recent years, nanocarrier-based pesticide delivery systems have provided new possibilities for the efficient utilization of pesticides. In this research, we developed a hydroxypropyl-β-cyclodextrin-modified graphene oxide (GO-HP-β-CD) nanocarrier for pyraclostrobin (Pyr) delivery and studied its application for tobacco target spot disease control. GO-HP-β-CD has excellent pesticide-loading performance for Pyr (adsorption capacity of 1562.5 mg/g) and good water dispersibility and stability. Besides, GO-HP-β-CD shows pH-responsive release performance. In addition, GO-HP-β-CD also has better leaf affinity than Pyr, and it can effectively adhere to the leaf surface after simulated washing. The results of antifungal experiments indicate that GO-HP-β-CD-Pyr has a good preventive effect on tobacco target spot disease, and its EC50 value is 0.384 mg/L, which is lower than Pyr. Specifically, this nanopesticide formulation does not contain toxic organic solvent or additive, so it has good environmental friendliness. Therefore, we believe that the GO-HP-β-CD-Pyr nanopesticide has brilliant potential in the prevention and control of tobacco diseases.

Magnetically actuated cisplatin-loaded nanoparticle collectives enhance drug penetration for potentiated ovarian cancer chemotherapy

Chemotherapy is the main clinical treatment for ovarian cancer, but still faces challenges of low drug targeting efficiency and insufficient drug permeability. Drug-loaded nanoparticle collectives, which are actuated by magnetic field, could be targeted to a designated location and achieve targeted drug delivery. In this work, we report a strategy that utilizes magnetic mesoporous silica nanoparticles loaded with cis-diaminodichloroplatinum (Fe3O4@SiO2-CDDP) for targeted delivery of chemotherapeutic drugs and enhances penetration into deep tumors. The Fe3O4@SiO2-CDDP collectives actively moved to the target tumor site, and this movement was regulated by a magnetic actuation system. Under the action of a torque-force hybrid magnetic field (TFMF), Fe3O4@SiO2-CDDP could further penetrate into the interior of tumors and achieve pH-responsive drug release in the tumor environment. The feasibility of this strategy was verified in three-dimensional cell spheres in vitro and in a tumor-bearing mouse model in vivo. This magnetically actuated nanoparticle collectives enhanced drug penetration strategy provides a new paradigm for targeted drug delivery and potentiated tumor therapy.

A bi-functional self-healing epoxy composite coating based on coordinated functionalized attapulgite/graphene oxide

Applications for graphene oxide (GO) in the field of corrosion protection will be severely constrained by the material’s poor dispersion and compatibility with epoxy resins, as well as the absence of self-healing corrosion protection in GO-based epoxy coatings. In this work, we developed a bi-functional 2-mercaptobenzothiazole (MBT) inhibitor-encapsulating GO-based nanocomposite (GAM) with pH-responsive release by implanting attapulgite (ATP) nanorods on the surface of GO. Additionally, GO-based nanocomposite can form covalent connections with epoxy resins and be evenly distributed in epoxy film via a ring opening process. Moreover, improved epoxy film compatibility and dispersion result in elevated mechanical strength and better impermeability, which prevent corrosion in both the active and passive modes. The corrosion resistance of GAM self-healing coating increased as the submersion period exceeded 24 h up to 0.54 M Ω cm2, resulting in the release of MBT inhibitor to form a passivation film at the defective region. Moreover, the improved charge transfer resistance (Rct) and the coating’s resistance to corrosive species (Rc) attribute to the self-healing ability of the GAM coating. The incorporation of GAM (2 %) nanocomposites into epoxy films enables long-term protection of AA2024-T3 by combining passive and self-healing corrosion prevention.

Hydrogels for Nucleic Acid Drugs Delivery.

Nucleic acid drugs are one of the hot spots in the field of biomedicine in recent years, and play a crucial role in the treatment of many diseases. However, its low stability and difficulty in target drug delivery are the bottlenecks restricting its application. Hydrogels are proven to be promising for improving the stability of nucleic acid drugs, reducing the adverse effects of rapid degradation, sudden release, and unnecessary diffusion of nucleic acid drugs. In this review, the strategies of loading nucleic acid drugs in hydrogels are summarized for various biomedical research, and classify the mechanism principles of these strategies, including electrostatic binding, hydrogen bond based binding, hydrophobic binding, covalent bond based binding and indirect binding using various carriers. In addition, this review also describes the release strategies of nucleic acid drugs, including photostimulation-based release, enzyme-responsive release, pH-responsive release, and temperature-responsive release. Finally, the applications and future research directions of hydrogels for delivering nucleic acid drugs in the field of medicine are discussed.

Interfacially Self-Assembled Mutifunctional Protein Thin Films for Accelerated Wound Healing.

The design of mutifunctional protein films for large-area spatially ordered arrays of functional components holds great promise in the field of biomedical applications. Herein, interfacial electrostatic self-assembly was employed to construct a large-scale protein thin film by inducing electrostatic interactions between three bovine serum albumin (BSA)-coated nanoclusters and cetyltrimethylammonium bromide (CTAB), leading to their spontaneous organization and uniform distribution at the oil-water interface. This protein film demonstrated excellent multienzyme functions, high antibacterial activity, and pH-responsive drug release capability. Therefore, it can accelerate the wound closure process through a synergistic effect that includes reducing local blood glucose levels, regulating cellular oxidative stress, eradicating bacteria, and promoting cell proliferation.

Illuminating the fight against breast cancer: Preparation and visualized photothermal therapy of hyaluronic acid coated ZIF-8 loading with indocyanine green and cryptotanshinone for triple-negative breast cancer

Triple-negative breast cancer (TNBC) is characterized by higher recurrence rate and mortality. Thermally-mediated ablation via photothermal therapy (PTT) demonstrates considerable promise for the eradication of breast cancer. Nonetheless, the efficacy of PTT is impeded by the thermal tolerance of tumor cells, which is attributed to the augmented expression of heat shock proteins (HSPs). These proteins, which function as ATP-dependent molecular chaperones, confer protection to cancer cells against the cytotoxic heat generated during PTT. Glycolysis is an important way for breast cancer cells to produce ATP, which can promote the occurrence and development of lung metastasis of breast cancer. Therefore, inhibiting glycolysis may diminish the expression of HSPs, curtail the growth of breast cancer, and prevent its metastasis. Glycolytic metabolism plays a pivotal role in the ATP biosynthesis within breast cancer cells, facilitating the progression and dissemination of pulmonary metastases. Consequently, targeting glycolysis presents a strategic approach to HSP expression, the proliferation of breast cancer, and impede its metastatic spread. Herein, we designed an indocyanine green (ICG) and cryptotanshinone (CTS) loaded hyaluronic acid (HA) coated Zeolitic Imidazolate Framework-8 (ZIF-8) drug delivery system. The drug delivery system had excellent photothermal properties, which could reach temperature sufficient for photothermal ablation of tumor cells. (ICG + CTS)@HA-ZIF-8 also showed pH-responsive drug release, enhancing the sustained release of ICG and CTS to extend their systemic circulation duration. Moreover, the HA modification of ZIF-8 served to augment its targeting capabilities both in vitro and in vivo, leveraging the enhanced permeation and retention (EPR) effect, as well as active tumor targeting via the CD44 receptor pathway, resulting in a higher drug concentration and a better therapeutic effect in tumor. (ICG + CTS)@HA-ZIF-8 could downregulate the expression of glycolysis-related protein pyruvate kinase-M2 (PKM2), thereby inhibiting the glycolysis process, further suppressing tumor cell energy metabolism, downregulating the expression of HSPs, overcoming tumor cell heat resistance, and improving PTT effect. It exhibited a notable suppressive impact on both the proliferation and migration of breast cancer cells, potentially offering innovative insights for the visualized PTT in breast cancer treatment.

Waterborne polyurethane nanoparticles incorporating linoleic acid as a potential strategy for controlling antibiotic resistance spread in the mammalian intestine

Plasmid-mediated conjugative transfer of antibiotic resistance genes (ARGs) within the human and animal intestine represents a substantial global health concern. linoleic acid (LA) has shown promise in inhibiting conjugation in vitro, but its in vivo effectiveness in the mammalian intestinal tract is constrained by challenges in efficiently reaching the target site. Recent advancements have led to the development of waterborne polyurethane nanoparticles for improved drug delivery. In this study, we synthesized four waterborne polyurethane nanoparticles incorporating LA (WPU@LA) using primary raw materials, including N-methyldiethanolamine, 2,2'-(piperazine-1,4-diyl) diethanol, isophorone diisocyanate, castor oil, and acetic acid. These nanoparticles, identified as WPU0.89@LA, WPU0.99@LA, WPU1.09@LA, and WPU1.19@LA, underwent assessment for their pH-responsive release property and biocompatibility. Among these, WPU0.99@LA displayed superior pH-responsive release properties and biocompatibility towards Caco-2 and IPEC-J2 cells. In a mouse model, a dosage of 10 mg/kg/day WPU0.99@LA effectively reduced the conjugation of IncX4 plasmids carrying the mobile colistin resistance gene (mcr-1) by more than 45.1-fold. In vivo toxicity assessment demonstrated that 10 mg/kg/day WPU0.99@LA maintains desirable biosafety and effectively preserves gut microbiota homeostasis. In conclusion, our study provides crucial proof-of-concept support, demonstrating that WPU0.99@LA holds significant potential in controlling the spread of antibiotic resistance within the mammalian intestine.

Metal ions-anchored bacterial outer membrane vesicles for enhanced ferroptosis induction and immune stimulation in targeted antitumor therapy

The activation of ferroptosis presents a versatile strategy for enhancing the antitumor immune responses in cancer therapy. However, developing ferroptosis inducers that combine high biocompatibility and therapeutic efficiency remains challenging. In this study, we propose a novel approach using biological nanoparticles derived from outer membrane vesicles (OMVs) of Escherichia coli for tumor treatment, aiming to activate ferroptosis and stimulate the immune responses. Specifically, we functionalize the OMVs by anchoring them with ferrous ions via electrostatic interactions and loading them with the STING agonist-4, followed by tumor-targeting DSPE-PEG-FA decoration, henceforth referred to as OMV/SaFeFA. The anchoring of ferrous ions endows the OMVs with peroxidase-like activity, capable of inducing cellular lipid peroxidation by catalyzing H2O2 to •OH. Furthermore, OMV/SaFeFA exhibits pH-responsive release of ferrous ions and the agonist, along with tumor-targeting capabilities, enabling tumor-specific therapy while minimizing side effects. Notably, the concurrent activation of the STING pathway and ferroptosis elicits robust antitumor responses in colon tumor-bearing mouse models, leading to exceptional therapeutic efficacy and prolonged survival. Importantly, no acute toxicity was observed in mice receiving OMV/SaFeFA treatments, underscoring its potential for future tumor therapy and clinical translation.

Tunicate cellulose nanocrystal reinforced multifunctional hydrogel with super flexible, fatigue resistant, antifouling and self-adhesive capability for effective wound healing

Hydrogels as skin wound dressings have been extensively studied owing to their good flexibility and biocompatibility. Nevertheless, the mechanical performance, adhesive capability, antifouling and antibacterial properties of conventional hydrogels are still unsatisfactory, which hinder the application of hydrogel for cutaneous healing. Here, we developed a novel biocompatible multifunctional hydrogel with super flexible, fatigue resistant, antifouling and self-adhesive capability for effective wound healing, where naturally rigid polymers including quaternized chitosan (QCS) and Tunicate cellulose nanocrystals (TCNCs) are used as bioactive cross-linkers and reinforcers to endow the hydrogel with excellent mechanical and antibacterial property, and the synergistic contributions from the poly(acrylic acid/methacrylate anhydride dopamine/sulfobetaine methacrylate) (poly(AA/DMA/SBMA)) chains and QCS endow the hydrogel with excellent adhesive property, antioxidant, antifouling and pH-responsive sustained drug release capabilities. The optimized hydrogel exhibited high tensile strength (77.69 KPa), large tensile strain (889.9 %), large toughness (307.51KJ.m−3), high adhesive strength (35.57 KPa) and ideal compressive property. The in vivo infected full-thickness skin model demonstrated that the hydrogel with vanvomycin sustained release ability efficiently improved the granulation tissue formation, facilitating collagen deposition and reducing inflammatory expression, thus effectively accelerating wound healing. This superiorly skin-adhesive antibacterial biocompatible hydrogel appears to be a promising candidate for wound therapy.

Synthesis, Optimization and Molecular Self-Assembly Behavior of Alginate-g-Oleylamine Derivatives Based on Ugi Reaction for Hydrophobic Drug Delivery.

To achieve the optimal alginate-based oral formulation for delivery of hydrophobic drugs, on the basis of previous research, we further optimized the synthesis process parameters of alginate-g-oleylamine derivatives (Ugi-FOlT) and explored the effects of different degrees of substitution (DSs) on the molecular self-assembly properties of Ugi-FOlT, as well as the in vitro cytotoxicity and drug release behavior of Ugi-FOlT. The resultant Ugi-FOlT exhibited good amphiphilic properties with the critical micelle concentration (CMC) ranging from 0.043 mg/mL to 0.091 mg/mL, which decreased with the increase in the DS of Ugi-FOlT. Furthermore, Ugi-FOlT was able to self-assemble into spherical micellar aggregates in aqueous solution, whose sizes and zeta potentials with various DSs measured by dynamic light scattering (DLS) were in the range of 653 ± 25~710 ± 40 nm and -58.2 ± 1.92~-48.9 ± 2.86 mV, respectively. In addition, RAW 264.7 macrophages were used for MTT assay to evaluate the in vitro cytotoxicity of Ugi-FOlT in the range of 100~500 μg/mL, and the results indicated good cytocompatibility for Ugi-FOlT. Ugi-FOlT micellar aggregates with favorable stability also showed a certain sustained and pH-responsive release behavior for the hydrophobic drug ibuprofen (IBU). Meanwhile, it is feasible to control the drug release rate by regulating the DS of Ugi-FOlT. The influence of different DSs on the properties of Ugi-FOlT is helpful to fully understand the relationship between the micromolecular structure of Ugi-FOlT and its macroscopic properties.

Hybrid Nanoparticles Based on Mesoporous Silica and Functionalized Biopolymers as Drug Carriers for Chemotherapeutic Agents.

Mesoporous silica nanoparticles (MSNs) are promising drug carriers for cancer therapy. Their functionalization with ligands for specific tissue/cell targeting and stimuli-responsive cap materials for sealing drugs within the pores of MSNs is extensively studied for biomedical and pharmaceutical applications. The objective of the present work was to establish MSNs as ideal nanocarriers of anticancer drugs such as 5-FU and silymarin by exploiting characteristics such as their large surface area, pore size, and biocompatibility. Furthermore, coating with various biopolymeric materials such as carboxymethyl chitosan-dopamine and hyaluronic acid-folic acid on their surface would allow them to play the role of ligands in the process of active targeting to tumor cells in which there is an overexpression of specific receptors for them. From the results obtained, it emerged, in fact, that these hybrid nanoparticles not only inhibit the growth of glioblastoma and breast cancer cells, but also act as pH-responsive release systems potentially useful as release vectors in tumor environments.

Bio-orthogonal click chemistry strategy for PD-L1-targeted imaging and pyroptosis-mediated chemo-immunotherapy of triple-negative breast cancer

BackgroundThe combination of programmed cell death ligand-1 (PD-L1) immune checkpoint blockade (ICB) and immunogenic cell death (ICD)-inducing chemotherapy has shown promise in cancer immunotherapy. However, triple-negative breast cancer (TNBC) patients undergoing this treatment often face obstacles such as systemic toxicity and low response rates, primarily attributed to the immunosuppressive tumor microenvironment (TME).Methods and resultsIn this study, PD-L1-targeted theranostic systems were developed utilizing anti-PD-L1 peptide (APP) conjugated with a bio-orthogonal click chemistry group. Initially, TNBC was treated with azide-modified sugar to introduce azide groups onto tumor cell surfaces through metabolic glycoengineering. A PD-L1-targeted probe was developed to evaluate the PD-L1 status of TNBC using magnetic resonance/near-infrared fluorescence imaging. Subsequently, an acidic pH-responsive prodrug was employed to enhance tumor accumulation via bio-orthogonal click chemistry, which enhances PD-L1-targeted ICB, the pH-responsive DOX release and induction of pyroptosis-mediated ICD of TNBC. Combined PD-L1-targeted chemo-immunotherapy effectively reversed the immune-tolerant TME and elicited robust tumor-specific immune responses, resulting in significant inhibition of tumor progression.ConclusionsOur study has successfully engineered a bio-orthogonal multifunctional theranostic system, which employs bio-orthogonal click chemistry in conjunction with a PD-L1 targeting strategy. This innovative approach has been demonstrated to exhibit significant promise for both the targeted imaging and therapeutic intervention of TNBC.Graphical abstract