Cancer has always posed a significant threat to human health, prompting extensive research into new treatment strategies due to the limitations of traditional therapies. Starvation therapy (ST) has garnered considerable attention by targeting the primary energy source, glucose, utilized by cancer cells for proliferation. Glucose oxidase (GOx), a catalyst facilitating glucose consumption, has emerged as a critical therapeutic agent for ST. However, mono ST alone struggles to completely suppress tumor growth, necessitating the development of synergistic therapy approaches. Metal catalysts possess enzyme-like functions and can serve as carriers, capable of combining with GOx to achieve diverse tumor treatments. However, ensuring enzyme activity preservation in normal tissue and activation specifically within tumors presents a crucial challenge. Nanodelivery systems offer the potential to enhance therapy effectiveness by improving the stability of therapeutic agents and enabling controlled release. This review primarily focuses on recent advances in the mechanism of GOx combined with metal catalysts for synergistic tumor therapy. Furthermore, it discusses various nanoparticles (NPs) constructs designed for synergistic therapy in different carrier categories. Finally, this review provides a summary of GOx-metal catalyst-based NPs (G-M) and offers insights into the challenges associated with G-M therapy, delivery design, and oxygen (O₂) supply.

PEG-poly(β-amino ester) (PEG-PBAE), which is an effective pH-responsive copolymer, was mainly synthesized by Michael step polymerization. Thioridazine (Thz), which was reported to selectively eliminate cancer stem cells (CSCs), was loaded into PEG-PBAE micelles (PPM) prepared by self-assembly at low concentrations. The critical micelle concentrations (CMC) of PPM in water were 2.49 μg/mL. The pH-responsive PBAE segment was soluble due to protonated tertiary amine groups when the pH decreased below pH 6.8, but it was insoluble at pH 7.4. The Thz-loaded PEG-PBAE micelle (Thz/PPM) exhibited a spherical shape, and the drug loading was 15.5%. In vitro release of Thz/PPM showed that this pH-sensitivity triggered the rapid release of encapsulated Thz in a weakly acidic environment. The in vitro cytotoxicity and cellular uptake of various formulations at pH 7.4 and 5.5 were evaluated on the mammospheres (MS), which were sorted by MCF-7 human breast cancer cell lines and identified to be a CD44⁺/CD24⁻ phenotype. The results of the cytotoxicity assay showed that blank micelles were nontoxic and Thz/PPM exhibited a similar anti-CSC effect on MS compared to Thz solution. Stronger fluorescence signal of Coumarin-6 (C6) was observed in MS treated by C6-loaded PPM (C6/PPM) at pH 5.5. The tumor inhibition rate and tumor weight of the free DOX and Thz/PPM groups were significantly different from those of the other groups, which free DOX and Thz/PPM effectively suppressed breast tumor growth in vivo. The above experimental results showed that Thz/PPM is an ideal and effective pH-responsive drug delivery carrier to a targeted therapy of CSCs.

Breast cancer is a major threat to safety and health of women. The breast cancer stem cells (BCSCs) have multi-drug resistance to chemotherapy drugs, which leads to chemotherapy failure. We proposed a strategy of delivery of tumor-killing drugs and a resistance reversal agent, to enhance inhibition of BCSCs. Here, schisandrin B (SchB)/AP NPs are constructed using acid-grafted-poly (β-amino ester) (ATRA-g-PBAE, AP) grafted polymer nanoparticle encapsulated SchB, with pH-sensitive release function. This drug delivery system has good pharmacological properties and can increase the SchB release with the decrease of pH. The NPs showed cytotoxic effects in reversing ATRA resistance to BCSCs. Lysosomal escape was achieved when the nanoparticles were taken up by BCSCs. In addition, we found that NPs may reverse MDR by inhibiting the expression of P-glycoprotein (P-gp) and affecting the energy supply of drug efflux. This study provides a nanodelivery therapy strategy that reverses BCSCs multidrug resistance (MDR) and demonstrates that it did so by interfering with cancer cell energy metabolism. Therefore, the co-delivery strategy of ATRA and SchB provides a new option for the treatment of breast cancer.

Bupleurum scorzonerifolium Willd. is a perennial herbaceous plant of the genus Bupleurum in the Apiaceae family. Also known as red Bupleurum, it is mainly distributed in Northeast China, North China and other regions and is a commonly used medicinal plant. It is difficult for the wild plant resources of Bupleurum scorzonerifolium Willd. to meet the market demand. In artificial cultivation, there are problems such as a low yield per plant, low quality, weakened stress resistance and variety degradation. The contents of bioactive components and metabolites in traditional Chinese medicinal materials vary significantly across different growth years. The growth duration directly impacts their quality and clinical efficacy. Therefore, determining the optimal growth period is one of the crucial factors in ensuring the quality of traditional Chinese medicinal materials. In this study, Gas Chromatography–Mass Spectrometry (GC-MS) and High-performance liquid chromatography (HPLC) were comprehensively applied to analyze the metabolically differential substances in different parts of Bupleurum scorzonerifolium Willd. By comparing the compositions and content differences of chemical components in different growth years and different parts, the chemical components with significant differences were accurately screened out. In order to further explore the dynamic change characteristics and internal laws of metabolites, a metabolic network was constructed for a visual analysis and, finally, to see the optimal growth years of Bupleurum scorzonerifolium Willd. This result showed that with the accumulation of the growth cycle, the height, root width, fresh mass and saikosaponins content of Bupleurum scorzonerifolium Willd. increased year by year. Except for sodium and calcium elements in the main shoot, the other elements were significantly reduced. In addition, 59 primary metabolites were identified by GC-MS, with the accumulation of the growth cycle, the contents of organic acids, sugars, alcohols and amino acids gradually decreased, while the contents of alkyl, glycosides and other substances gradually increased. There were 53 positive correlations and 18 negative correlations in the triennial Bupleurum scorzonerifolium Willd. grid, all of which were positively correlated with saikosaponins. Therefore, the triennial Bupleurum scorzonerifolium Willd. was considered to be the suitable growth year. It not only provided a new idea and method for the quality evaluation of Bupleurum scorzonerifolium Willd., but also provided a scientific basis for the quality control of Chinese herbs.

Background/Objectives: Goupi plaster (GP) is a traditional black plaster composed of a biphasic fibrous–oil matrix containing multiple bioactive compounds, and it has been widely used for the treatment of musculoskeletal disorders. Representative active compounds include sinomenine, osthole, cinnamaldehyde, and imperatorin, which exhibit anti-inflammatory and analgesic effects. However, due to its heterogeneous matrix structure and multi-component nature, the pharmaceutical delivery behavior of GP remains difficult to evaluate using conventional methods. Therefore, this study aimed to establish an integrated structure–release–permeation–pharmacokinetic evaluation framework to systematically characterize the transdermal delivery behavior of GP. Methods: GP was evaluated using multi-level analysis, including microstructural imaging (FESEM), in vitro release, ex vivo skin permeation, and in vivo dual-site microdialysis. Four representative bioactive compounds (sinomenine, osthole, cinnamaldehyde, and imperatorin) were selected as marker compounds. Release data were fitted to kinetic models, and structure–release relationships were examined using the Higuchi release constant (k_h). Skin-barrier alterations were assessed by attenuated total reflectance–Fourier transform infrared spectroscopy (ATR–FTIR) and differential scanning calorimetry (DSC). Local concentrations in subcutaneous (SC) and intra-articular (IA) compartments were measured by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) to explore potential in vitro–in vivo correlation (IVIVC). Results: FESEM revealed a fibrous–oil network structure. GP exhibited sustained, diffusion-dominated release, with k_h = 0.9908–0.9977 and Korsmeyer–Peppas (K–P) release exponents (n) = 0.61–0.66, differing from active pharmaceutical ingredient (API) controls. Fiber area fraction and fiber length density showed negative correlations with k_h (r = −0.91 to −0.99); ex vivo permeation profiles varied among compounds, and ATR–FTIR and DSC analyses showed moderate changes in skin-barrier properties. Dual-site microdialysis demonstrated sustained local exposure, and a positive relationship was observed between in vitro release and in vivo concentrations. Conclusions: This study establishes an integrated structure–release–permeation–pharmacokinetic evaluation framework for traditional black plaster systems. The observed IVIVC is descriptive rather than predictive, reflecting a trend-level association under the current experimental conditions. These findings highlight the importance of integrating in vitro release, skin permeation, and local pharmacokinetics for understanding drug delivery behavior in complex transdermal matrix systems, and provide a methodological basis for quality consistency evaluation of traditional black plaster formulations.