This innovative nanoplatform combines active targeting, stimuli-responsive drug release, and chemo-chemodynamic therapy (CCDT), presenting a promising approach to overcome drug resistance and improve the treatment of OSCC.
Abstract
This study tackles key challenges in oral squamous cell carcinoma (OSCC) chemotherapy, such as poor targeting, systemic toxicity, and drug resistance. We developed a pH-responsive, targeted nanoplatform (CP@Cu-Z@P-G) based on copper-doped zeolitic imidazolate framework-8 (Cu-ZIF-8). The nanoplatform was functionalized with an Epidermal Growth Factor Receptor (EGFR)-specific ligand (PEG-GE11) for active tumor targeting and designed to degrade in the acidic tumor microenvironment, enabling the synchronous release of cisplatin (CDDP) and plumbagin (PLB). The released copper ions (Cu2+) disrupt intracellular redox homeostasis via glutathione (GSH) depletion and catalyze Fenton-like reactions to generate hydroxyl radicals (˙OH). These radicals act synergistically with PLB-induced reactive oxygen species (ROS) to augment oxidative stress, thereby sensitizing tumor cells to CDDP. In vitro experiments confirmed the pH-responsive drug release profile of the nanoplatform under simulated tumor microenvironment conditions. In vivo imaging studies demonstrated that EGFR-targeted modification significantly enhanced nanoparticle accumulation in tumor sites. Treatment with CP@Cu-Z@P-G exhibited potent antitumor efficacy with minimal systemic toxicity. Thus, this innovative nanoplatform combines active targeting, stimuli-responsive drug release, and chemo-chemodynamic therapy (CCDT), presenting a promising approach to overcome drug resistance and improve the treatment of OSCC.
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
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
Current clinical interventions for solid tumors are confronted with multiple prominent challenges, including intratumoral hypoxia, constitutively activated endogenous antioxidant defense systems, and inefficient tumor targeting. In this study, a multifunctional nanoliposome carrier is developed by co-encapsulation of hemoglobin (Hb), ferric citrate (FC), and chlorin e6 (Ce6), and surface-modified with the iRGD (CRGDKGPDC) peptide to facilitate active tumor targeting and enhance subsequent intratumoral penetration. Under ultrasound irradiation, the iRGD-targeted nanoliposomes can efficiently generate two distinct types of reactive oxygen species (ROS) to produce strong synergistic cytotoxicity against 4T1 breast cancer cells via separate pathways: singlet oxygen (1O₂) through the sonodynamic therapy (SDT) pathway, and hydroxyl radicals (·OH) through the chemodynamic therapy (CDT) pathway. In vivo experimental results show that tail vein injection (i.v.) of iRGD-targeted nanoliposomes combined with external ultrasound irradiation achieves can significantly enhance tumor growth inhibition, which is attributed to triggered on-demand drug release induced by ultrasound. The as-prepared iRGD-targeted nanoliposomes exhibit remarkable synergistic antitumor efficacy, inducing extensive tumor necrosis, apoptosis, and ferroptosis while causing minimal systemic side effects, demonstrating great application potential for future breast cancer therapy.
Runming Zhong, Yingzhe Wu, Yanzhen Lou et al.· Colloids and Surfaces B: Bio...· 0 citations
AIMS
Breast cancer (BC) remains the most prevalent malignancy in women, with conventional chemotherapy limited by drug resistance. This study develops a glutathione (GSH)-responsive nanoplatform combining chemotherapy with phototherapy against drug-resistant BC.
METHODS
Gambogic acid (GA) was conjugated to carboxymethyl chitosan via disulfide bonds (GA-SS-CMCS, GSC), then loaded with graphene quantum dots (GQDs) to form GSC@GQD nanocomposites. The formulation was characterized by TEM, DLS, and NMR; photothermal performance, drug release, ROS generation, hemocompatibility, and anti-tumor efficacy were evaluated in MCF-7, MCF-7/ADR cells and MCF-7/ADR xenografts.
RESULTS
GSC@GQD showed uniform morphology (~180 nm), GSH-triggered GA release (94% at 48 h), and hemolysis <5%. Under 808 nm irradiation, GSC@GQD raised temperature by 20 °C (vs. 9 °C for free GQDs), induced intracellular ROS accumulation, and achieved apoptosis rates of 86% (MCF-7) and 76% (MCF-7/ADR). In vivo, GSC@GQD + NIR suppressed tumor growth with satisfactory biosafety.
CONCLUSIONS
GSC@GQD integrates chemotherapy, photodynamic and photothermal therapy into a GSH-responsive platform, offering a promising strategy against drug-resistant BC.
This nanoplatform integrates CPT chemotherapy, selenium intervention, and the p53 mutation background into a single system, establishing a toxicity-controlled, efficacy-enhanced strategy and reveals how selenium-based nanomaterials remodel redox homeostasis, bypass p53 deficiency, and reprogram apoptotic networks.
Cuiman Tang, Zhongjuan Wang, Yankun Liu et al.· ACS Nano· 0 citations
A dual-functional self-assembled nanoplatform integrating PDT and selective uPA inhibition for synergistic CRC treatment achieves short-term acute tumor ablation via PDT and sustained anti-metastatic potential via uPA inhibition within the tested observation windows, with favorable biosafety.
