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Chemotherapy-induced Organ Toxicity Mitigation · Journal article
Pharmaceutics · September 8, 2026
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This is a preclinical feasibility and efficacy study of a novel pH-responsive hydrogel nanoparticle platform combining echinacoside-copper metal–phenolic networks and diallyl trisulfide for vaginal delivery to cervical tumors. In an orthotopic mouse model, the formulation achieved 87.81% tumor inhibition, superior to controls, with no apparent systemic toxicity; however, the study is limited to animal models and surrogate mechanistic endpoints, with no human efficacy or safety data.
Preclinical efficacy study (orthotopic xenograft model and in vitro cell culture). SiHa and HeLa cervical cancer cell lines; orthotopic cervical cancer model established in animals (species and number not specified).. Intervention: ECD nanoparticles (echinacoside-copper metal–phenolic networks loaded with diallyl trisulfide) incorporated into poloxamer/HPMC thermosensitive hydrogel for vaginal delivery.. Compared with: Free diallyl trisulfide and blank metal–phenolic network hydrogel (in vivo); untreated controls in cell viability assays (implied but not explicitly stated)..
ECD nanoparticles showed uniform size of ~135 nm and DATS loading of ~27.6% pH-responsive release: 16.4% at pH 7.4 (vaginal), 80.9% at pH 5.6 (lysosomal) over 24 hours In orthotopic cervical cancer model, ECD NPs hydrogel achieved tumor inhibition rate of 87.81%, significantly outperforming free DATS (65.3%) and blank MPN hydrogel (55.62%)
Systemic toxicity assessed only by histology; pharmacokinetics, biodistribution, and organ-level safety markers not detailed No evident systemic toxicity observed in vivo
This work demonstrates a promising proof-of-concept for local delivery of a dual-mechanism anticancer agent via a pH-responsive vaginal hydrogel. Translation to clinical use would require human feasibility studies, pharmacokinetics, and randomized controlled trials to confirm efficacy and assess safety in cervical cancer patients.
A single-center preclinical efficacy study in an orthotopic mouse model with promising tumor inhibition but no human data, safety data limited to histology, and mechanism demonstrated only in cell culture.
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This work demonstrates a promising proof-of-concept for local delivery of a dual-mechanism anticancer agent via a pH-responsive vaginal hydrogel. Translation to clinical use would require human feasibility studies, pharmacokinetics, and randomized controlled trials to confirm efficacy and assess safety in cervical cancer patients.
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Background/Objectives: Cervical cancer cells evade chemotherapy by upregulating antioxidant defenses (e.g., glutathione (GSH)). A platform that simultaneously amplifies ROS and suppresses antioxidant defense is a low toxicity strategy. This study presents a local nanoplatform that combines chemodynamic therapy (CDT) with chemotherapy for the localized treatment of cervical cancer. Methods: Diallyl trisulfide (DATS) was loaded into the echinacoside (ECH)-copper metal–phenolic networks (MPNs) nanoparticles (ECD NPs) through a one-step coordination assembly method. The nanoparticles were incorporated into a poloxamer/HPMC thermosensitive hydrogel for vaginal delivery. The formulation was characterized for size, drug loading, sol–gel transition, and pH-responsive release. Antitumor activity was evaluated in SiHa and HeLa cells via Cu2+ uptake, GSH depletion, ROS accumulation, apoptosis markers, and viability. In vivo efficacy and biosafety were assessed in an orthotopic cervical cancer model. Results: ECD NPs showed uniform size (~135 nm), high DATS loading (~27.6%). The ECD NPs-loaded hydrogel exhibited a sol–gel transition at 36.7 °C. The ECD NPs-loaded hydrogel released 16.4% of DATS at pH 7.4, 32.4% at pH 4.5, 64.8% at pH 6.5, and 80.9% at pH 5.6 over 24 h. Release was minimal at vaginal pH, clearly triggered at tumor pH, and fastest at lysosomal pH, confirming pH-responsive behavior. The ECD NPs-loaded hydrogel enhanced Cu2+ uptake, depleted GSH, elevated ROS, and reduced cell viability to <50% at 80 μg/mL. In the orthotopic model, the ECD NPs hydrogel achieved a tumor inhibition rate of 87.81%, significantly outperforming free DATS (65.3%) and blank MPN (55.62%) hydrogels, with no evident systemic toxicity. Conclusions: The ECD NPs hydrogel triggers a Cu2+-driven ROS/GSH cascade that combines copper-mediated oxidative stress with DATS-induced apoptosis for enhanced antitumor activity. Its vaginal localization, pH-responsive release, and biosafety profile support further evaluation for cervical cancer therapy.
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