Aug 2026· ACS Applied Nano Materials· Vol 9, pp. 16501-16513· 0 citations· 37 references
TL;DR
A glutathione (GSH)-responsive biomimetic nanoplatform, termed CMnMG, is developed for magnetic resonance (MR) imaging and gemcitabine (GEM) chemotherapy and T1-weighted MR imaging of pancreatic cancer.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains difficult to treat because of inefficient intracellular drug delivery and robust redox defense. Here, we developed a glutathione (GSH)-responsive biomimetic nanoplatform, termed CMnMG, for magnetic resonance (MR) imaging and gemcitabine (GEM) chemotherapy. CMnMG was prepared by loading GEM into manganese-doped mesoporous silica nanoparticles and coating them with SW1990 pancreatic-cancer-cell membranes. The membrane coating enhanced homologous tumor cell uptake and reduced macrophage internalization. After cellular uptake, GSH triggered the degradation of the manganese-containing framework, leading to GSH consumption and the release of GEM and Mn2+. This process increased intracellular drug availability and weakened antioxidant defenses. Released Mn2+ also promoted reactive oxygen species generation in the presence of endogenous H2O2, thereby enhancing the GEM-induced cytotoxicity. Meanwhile, paramagnetic Mn2+ increased the T1-weighted MR contrast. Thus, CMnMG therefore offers a GSH-responsive strategy for improving GEM chemotherapy and T1-weighted MR imaging of pancreatic cancer.
A TME-responsive nanoplatform composed of MPDA core shielded by manganese dioxide (MnO2) shell, enabling sequential co-delivery of doxorubicin and resveratrol for chemo-/chemodynamic/photothermal therapy, offering a promising paradigm for overcoming chemoresistance in bladder cancer.
Zhihua Zeng, Chao Hu, Yihe Li et al.· Colloids and Surfaces B: Bio...· 0 citations
Due to high systemic toxicity associated with conventional chemotherapy and limited drug accumulation at the tumour site, pancreatic cancer is still challenging to eliminate. To improve the intracellular transport of capecitabine, a glutathione-responsive nanocarrier system based on poly(lactic-co-glycolic acid) (PLGA) was designed. PLGA coupled with cystamine was used to create the nanoformulation, which introduced disulphide bonds that are stable in extracellular environments but cleaved in a reductive intracellular environment enriched with glutathione. This redox-sensitive mechanism enables rapid drug release specifically within cancer cells. The nanoparticle surface was functionalised with folic acid to promote folate receptor-mediated endocytosis, which is often overexpressed on pancreatic cancer, thereby further enhancing cellular uptake. DLS and TEM Microscopy confirmed a consistent nanoparticle size of FoA-PLGA-Cys-CAP 261.3 ± 2.8 nm with uniform shape, indicating suitability for therapeutic delivery. In vitro cytotoxicity studies showed an IC50 value of 77.52 ± 1.33 μg/mL and increased reactive oxygen species generation in treated cells. For in vivo evaluation, PANC1 cells were subcutaneously implanted to establish a pancreatic tumour model. Over 12 days, tumour size increased from 20.617 mm2 to 57.71 mm2. Following 10 days of treatment with the nanoformulation, tumour size significantly decreased from 57.71 mm2 to 43.099 mm2, demonstrating promising therapeutic efficacy.
Abhay Dev Tripathi, S. Katiyar, Vivek K. Chaturvedi et al.· Journal of drug targeting (P...· 0 citations
Dense stromal barriers and lysosomal sequestration severely restrict the extracellular transport and intracellular trafficking of nanomedicines in pancreatic cancer, while the robust glutathione (GSH)-dependent antioxidant defense further compromises therapeutic efficacy. Here, we developed a proton sponge-enabled dual-driven nanomotor, HA/PEI-DOX@MMSN@Pt (HPDMP), for MRI-guided pancreatic cancer therapy. The asymmetric Pt domain generated near-infrared (NIR)-induced self-thermophoretic motion as the principal externally controllable driving mechanism, whereas endogenous H2O2 provided auxiliary catalytic propulsion, together facilitating nanomotor transport through the dense tumor stroma and enhancing intratumoral penetration. Following cellular uptake, PEI-mediated proton sponge activity facilitated lysosomal escape and increased cytosolic DOX availability. Meanwhile, tumor-microenvironment-responsive degradation of the Mn-doped framework consumed GSH and released Mn2+, thereby enhancing reactive oxygen species (ROS) generation, ferroptosis-associated oxidative damage, and T1-weighted MRI contrast. HA modification further promoted CD44-mediated tumor targeting. Under NIR irradiation, HPDMP achieved pronounced antitumor efficacy with favorable biosafety. This work provides a barrier-oriented nanomotor strategy for pancreatic cancer therapy.
Shuai He, Fulin Li, Pan Yang et al.· Advanced Healthcare Material...· 0 citations
Glioblastoma multiforme (GBM) remains one of the most aggressive central nervous system malignancies, with therapeutic efficacy severely constrained by the blood-brain barrier (BBB), which limits drug delivery to the tumor site, and by the lack of tumor-specific targeting, leading to off-target effects and inadequate intratumoral accumulation. To address these interconnected challenges, we designed a dual-targeted biomimetic nanoplatform (GIM@Lip-Bio/FA) using glycogen as a biodegradable core for co-loading methotrexate (MTX) and IR780, followed by coating with a lipid layer sequentially modified with biotin and folic acid (FA) to enable active transport across the BBB and selective recognition by glioma cells. The resulting nanoparticles exhibited a uniform size, excellent stability, and significantly enhanced cellular uptake mediated by SMVT and folate receptor α (FRα). Notably, the nanoplatform demonstrated efficient BBB penetration and precise tumor accumulation in orthotopic GBM models. Upon near-infrared irradiation, synergistic chemo-photothermal therapy was achieved, leading to effective suppression of tumor growth, with a 76% reduction in tumor volume compared to the control group. This work presents a promising strategy for targeted GBM therapy.
Yumeng Bao, Junsong Guo, Hao Li et al.· Nanoscale· 0 citations
Superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as promising theranostic agents owing to their magnetic hyperthermia efficiency and capability as magnetic resonance imaging (MRI) contrast agents. However, achieving sufficient intracellular iron accumulation remains a critical challenge for effective therapy. In this study, we report the development of cancer cell membrane-coated SPIONs (CM-SPIONs) to enhance tumor targeting and intracellular delivery. The CM-SPIONs were prepared using a modified Bangham method in the presence of membranes derived from 4T1 triple-negative breast cancer cells. The resulting nanoparticles exhibited significantly enhanced cellular uptake, reaching an intracellular iron concentration of 6 μg [Fe]/106 cells after 24 h incubation, representing a fivefold increase compared to uncoated SPIONs. Fluorescence imaging revealed predominant localization within lysosomes in the perinuclear region, suggesting that the lysosomal compartment may contribute to the observed AMF-induced cytotoxicity. Upon exposure to an alternating magnetic field (AMF) for 45 min, the CM-SPIONs resulted in 78.6% inhibition of cell proliferation, which was markedly higher than uncoated SPIONs. Furthermore, incubation with CM-SPIONs (0.05 mg [Fe]/mL, 3 h) reduced the T2 relaxation time from 2.71 s in the untreated cell suspension to 0.48 s, demonstrating significant MRI contrast enhancement. These results indicate that the CM-SPIONs represent a promising platform integrating magnetic hyperthermia with MRI-based cancer theranostics.
By integrating receptor-mediated targeting, redox homeostasis disruption, and chemosensitization, MnO2@Man/DOX offers a promising metabolism-oriented strategy for treating refractory TNBC.
Guanghui Mei, Hanwen Wang, Xinhua Lin et al.· Nanomedicine: Nanotechnology...· 0 citations
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