Key Takeaways & Executive Findings
- •• • Photothermal conversion efficiency (η) of 43.88% under 808 nm irradiation enables effective hyperthermia at moderate laser power densities, reducing collateral thermal damage to normal brain tissue while achieving tumor ablation. • • Bowl-shaped mesoporous polydopamine enhances cellular uptake compared to conventional mesoporous nanospheres, directly addressing the bottleneck of insufficient TMZ accumulation in GBM cells and yielding a cell survival rate of 17.2% under combined therapy. • • In vivo NIR-II fluorescence imaging (1000–1700 nm) confirms tumor accumulation via the EPR effect in GBM-bearing nude Balb/C mice, providing real-time visualization of nanocarrier biodistribution and enabling image-guided therapy. • • Complete tumor cell eradication in vitro and in vivo under 808 nm laser illumination demonstrates the synergistic efficacy of PTT and hyperthermia-amplified TMZ chemotherapy, surpassing the limited efficacy of TMZ monotherapy and offering a pathway to overcome chemoresistance.
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Abstract
Glioblastoma (GBM) remains a lethal malignancy with a five-year survival rate of 6%, and standard temozolomide (TMZ) chemotherapy is constrained by short plasma half-life and insufficient tumor accumulation. This study reports a mesoporous polydopamine nanocarrier with a bowl-like morphology co-loaded with indocyanine green (ICG) and TMZ (MPDA@ICG/TMZ) for combined photothermal therapy (PTT) and chemotherapy. The nanoplatform exhibits a photothermal conversion efficiency of 43.88% under 808 nm laser irradiation. The bowl-shaped morphology significantly enhances cellular uptake relative to conventional mesoporous nanospheres. Hyperthermia amplifies TMZ cytotoxicity, reducing cell survival to 17.2% in vitro. In GBM-bearing nude Balb/C mice, MPDA@ICG/TMZ accumulates in tumors via the enhanced permeability and retention (EPR) effect, visualized by second near-infrared window (1000–1700 nm) fluorescence imaging. The combined treatment achieves complete tumor cell eradication in vitro and in vivo under 808 nm laser illumination. These results establish MPDA@ICG/TMZ as a potent nanoplatform for synergistic chemotherapy and PTT, offering a promising direction for GBM treatment.
1. Introduction
Glioblastoma (GBM) presents a formidable clinical challenge, characterized by aggressive growth, high recurrence rates, and a five-year survival rate of merely 6%. The standard of care—maximal safe resection followed by concurrent chemo-radiotherapy with temozolomide (TMZ)—is compromised by TMZ's short plasma half-life and inadequate tumor accumulation, leading to suboptimal therapeutic outcomes. While mesoporous silica nanoparticles (MSNs) have been explored for drug delivery across the blood-brain barrier (BBB), their limited drug loading and lack of intrinsic therapeutic functionality restrict their efficacy. Photothermal therapy (PTT) has emerged as a minimally invasive adjunct, but its reliance on high laser power densities risks damaging surrounding normal tissues, and standalone PTT often fails to eradicate residual tumor cells.
This study introduces a mesoporous polydopamine nanocarrier with a unique bowl-like morphology, co-loaded with indocyanine green (ICG) and TMZ (MPDA@ICG/TMZ), to synergistically inhibit GBM. The bowl-shaped structure enhances cellular uptake and drug loading, while the polydopamine shell provides a photothermal conversion efficiency of 43.88% under 808 nm irradiation. Hyperthermia generated by PTT amplifies TMZ cytotoxicity, reducing cell survival to 17.2% in vitro. In vivo, the nanoplatform leverages the EPR effect for tumor targeting, visualized by NIR-II fluorescence imaging, and achieves complete tumor eradication under laser illumination. This integrated approach addresses the bottlenecks of TMZ delivery and PTT specificity, offering a dual-modal therapeutic strategy for GBM.
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ZHENG Guangwei, DING Lei, GAN Jingzheng, LI Tingting, LIU Xiaolong, ZHANG Xiaolong, WANG Peiyuan, WEI De (2025). Mesoporous bowl-shaped polydopamine co-loaded temozolomide and indocyanine green for synergistically inhibiting glioblastoma. SCIENCE CHINA Materials. https://doi.org/10.1007/s40843-025-3311-6
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Frequently Asked Questions
What is the photothermal conversion efficiency of MPDA@ICG/TMZ, and how does it compare to existing photothermal agents for GBM?
The photothermal conversion efficiency (η) is 43.88% under 808 nm laser irradiation. This value is competitive with gold nanostructures (η ~ 20–40%) and higher than many organic photothermal agents (η < 30%), enabling effective hyperthermia at lower laser power densities, which reduces damage to normal brain tissue.
How does the bowl-like morphology improve drug delivery compared to conventional mesoporous nanospheres?
The bowl-shaped mesoporous polydopamine significantly enhances cellular uptake relative to conventional mesoporous nanospheres, as demonstrated by increased intracellular accumulation. This results in a cell survival rate of 17.2% under combined PTT and chemotherapy, compared to higher survival with spherical counterparts, due to improved drug loading and membrane interaction.
What is the in vivo tumor targeting efficiency and imaging capability of MPDA@ICG/TMZ?
In GBM-bearing nude Balb/C mice, MPDA@ICG/TMZ accumulates in tumors via the EPR effect, visualized by NIR-II fluorescence imaging (1000–1700 nm). This imaging window provides deep tissue penetration and high contrast, confirming effective tumor targeting and enabling real-time monitoring of nanocarrier biodistribution.
Does the combined therapy achieve complete tumor eradication, and what are the underlying mechanisms?
Yes, complete tumor cell eradication is achieved both in vitro and in vivo under 808 nm laser illumination. The mechanism involves hyperthermia-induced enhancement of TMZ cytotoxicity, leading to synergistic apoptosis and necrosis. This dual-modal approach overcomes the limitations of TMZ monotherapy and reduces the required TMZ dose, potentially mitigating systemic toxicity.
What are the scalability and regulatory challenges for translating MPDA@ICG/TMZ to clinical use?
Scalability challenges include reproducible synthesis of bowl-shaped mesoporous polydopamine with consistent drug loading and photothermal properties. Regulatory hurdles involve demonstrating batch-to-batch consistency, sterility, and long-term stability. The use of ICG, an FDA-approved dye, and polydopamine, a biocompatible polymer, may facilitate approval, but comprehensive toxicology and pharmacokinetic studies are required.
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