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Cancer, Hypoxia, and Metabolism / Nanoplatforms for Cancer Theranostics · Journal article
Small · August 10, 2026
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This work describes rational design and synthesis of magnetic metal–organic framework nanocomposites achieving 98% doxorubicin loading efficiency in vitro. In glioblastoma and breast cancer cell lines, AMF exposure of drug-loaded particles induced lysosomal permeabilization and enhanced cytotoxicity without bulk heating, suggesting a novel intracellular activation mechanism. However, the study is confined to materials characterization and cell culture; no pharmacokinetics, biodistribution, in vivo efficacy, safety, or translation pathway is provided.
In vitro materials synthesis and cell culture study. Glioblastoma and breast cancer cell lines (species and strain not specified). Intervention: Magnetic metal–organic framework nanocomposites (cubic iron oxide core, ZIF-8 shell, doxorubicin-loaded) with alternating magnetic field exposure. Compared with: Doxorubicin-loaded composites without AMF exposure; control conditions not fully specified.
Cubic iron oxide nanoparticle cores with ZIF-8 shell achieved superior MHT performance compared to spherical cores In-situ encapsulation of doxorubicin during ZIF-8 growth achieved 98% loading efficiency AMF-exposed doxorubicin-loaded composites induced lysosomal permeabilization and enhanced cytotoxicity in glioblastoma and breast cancer cells
No in vivo efficacy, biodistribution, or pharmacokinetic data Sample sizes and statistical analysis methods for cytotoxicity assays not stated
This is a proof-of-concept platform study with no immediate clinical application. Substantial additional work—including in vivo efficacy, systemic toxicology, pharmacokinetics, and mechanism of action studies—would be required before clinical translation could be considered.
Early-stage in vitro characterization of a novel nanoparticle platform with drug loading and cell culture data, but no in vivo efficacy, pharmacokinetics, toxicology, or clinical translation reported.
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This is a proof-of-concept platform study with no immediate clinical application. Substantial additional work—including in vivo efficacy, systemic toxicology, pharmacokinetics, and mechanism of action studies—would be required before clinical translation could be considered.
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ABSTRACT A seeded growth strategy was developed to synthesize core–shell magnetic metal–organic framework (MOF) composites for magnetic hyperthermia (MHT) and MHT‐triggered drug delivery. Cubic or spherical iron oxide nanoparticles, with nanocubes selected for their superior MHT performance, were coated with cetyltrimethylammonium bromide to enable aqueous ZIF‐8 shell growth. Shell thickness strongly influenced heating efficiency under alternating magnetic fields (AMFs), with thinner shells and cubic cores yielding enhanced MHT performance. Doxorubicin (Doxo) was used as a model chemotherapeutic drug and loaded either by surface adsorption or via in‐situ encapsulation during ZIF‐8 growth, the latter achieving an exceptional loading efficiency of 98%. To ensure stability in physiological environments, an amphiphilic polymer coating was applied, improving dispersion while regulating shell degradation and drug release. Doxo‐loaded composites exhibited efficient cellular uptake and lysosomal localization in glioblastoma and breast cancer cells. Confocal microscopy revealed that magnetic field exposure induced lysosomal permeabilization and redistribution of Doxo, indicating a potential lysosomal escape mechanism. Notably, enhanced cytotoxicity occurred only when AMFs were applied to Doxo‐loaded composites, despite no measurable bulk temperature increase, suggesting localized MHT‐induced intracellular damage. Overall, shell‐tunable magnetic‐MOF nanohybrids emerge as promising platforms for controlled, heat‐free intracellular drug activation for targeted cancer therapy.
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