Key Takeaways & Executive Findings
- •• • Mesopore size of 4.4 nm achieved a gemcitabine loading of 228 mg g−1, a 3.7-fold increase in combined therapy cytotoxicity over monotherapy, and >70% drug release under NIR irradiation, demonstrating the critical balance between pore architecture and therapeutic payload. • • Photothermal conversion efficiency reached 62% via N-doping and defect engineering, enabling NIR-triggered hyperthermia that enhances tumor permeability and drug release kinetics. • • Biocompatibility exceeded 95% cell viability at 200 μg mL−1, while combined therapy reduced tumor cell viability to ~5% at 25 μg mL−1, indicating a wide therapeutic window and potent antitumor efficacy. • • Pore size control via kinetic modulation of resin polymerization and TEOS hydrolysis allows scalable synthesis of mC with tunable mesopores (2-5 nm), directly linking structural parameters to functional performance in photothermal-chemotherapy.
Abstract
Carbon-based materials have gained significant attention in anticancer treatment due to their exceptional biocompatibility, yet critical challenges persist in establishing definitive correlations between their porous structures and functional performance. We report the use of a silica template to guide pore formation in the design of mesoporous carbon spheres (mC) with tailored pore structures for improved combined photothermal-chemotherapy. The mesopore size of mC was adjusted by kinetic control of resin polymerization and silica hydrolysis. Structural characterization showed that 4.4 nm mesopores enabled an exceptional gemcitabine loading of 228 mg g−1 and a sustained pH/thermal dual-responsive release with >70% drug release under near-infrared (NIR) irradiation. Finite element analysis demonstrated pore size-dependent heat transfer dynamics, with the improved mC achieving a superior photothermal conversion efficiency of 62% by a combination of N-doping and defect engineering. In vitro evaluations confirmed outstanding biocompatibility with >95% cell viability at 200 μg mL−1 and potent tumor suppression in pancreatic and biliary cancer models with an ~5% cell viability at 25 μg mL−1 where combined therapy showed a 3.7-fold increased cytotoxicity over monotherapy. The improved structure of mC facilitated cascade therapeutic effects with enhanced tumor permeability derived from NIR-triggered hyperthermia and prolonged therapeutic exposure due to pH-responsive drug release. This pore engineering strategy establishes a structure-function process for next-generation theranostic platforms, addressing the critical limitations of conventional pancreatic and biliary cancer therapies through spatiotemporal control of multimodal treatment.
1. Introduction
Conventional chemotherapy for pancreatic and biliary cancers suffers from off-target toxicity and suboptimal intratumoral drug accumulation due to nonspecific biodistribution. Photothermal therapy (PTT) offers spatiotemporal control but is limited by tumor heterogeneity-induced thermal resistance and heat shock protein-mediated protection, often failing to achieve complete eradication. The integration of PTT with chemotherapy aims to enhance drug penetration and induce thermosensitization, yet existing drug delivery platforms lack precise control over pore architecture to optimize synergistic effects.
This work addresses the bottleneck by engineering mesoporous carbon spheres (mC) with tailored pore sizes via silica templating and kinetic control. The 4.4 nm mesopores achieve high drug loading (228 mg g−1) and dual-responsive release, while N-doping and defect engineering boost photothermal conversion to 62%. This structure-function correlation provides a blueprint for adaptive carbon-based cancer therapeutics, overcoming the limitations of conventional therapies through spatiotemporal control of multimodal treatment.
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LIU Pengxiang, DU Juan, CHEN Aibing, HOU Senlin (2026). Engineered mesoporous carbon spheres with tailored pore structures for improved photothermal-chemotherapy. New Carbon Materials. https://doi.org/10.1016/S1872-5805(25)61033-X
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Frequently Asked Questions
What is the optimal mesopore size for balancing drug loading and photothermal conversion, and how was it determined?
The optimal mesopore size was 4.4 nm, which achieved a gemcitabine loading of 228 mg g−1 and a photothermal conversion efficiency of 62%. This was determined through structural characterization and finite element analysis, showing that smaller pores (2-5 nm) enhance drug loading but larger pores improve photothermal effects. The 4.4 nm size balanced both properties, enabling efficient combined therapy.
How does the dual-responsive drug release (pH and thermal) function under physiological conditions, and what are the release kinetics?
The mC system exhibits sustained pH/thermal dual-responsive release, with >70% drug release under NIR irradiation. The release is triggered by acidic tumor microenvironment (pH-responsive) and hyperthermia (thermal-responsive), enabling targeted release at tumor sites. This dual mechanism prolongs therapeutic exposure and enhances tumor permeability.
What is the scalability of the synthesis method for industrial production?
The synthesis uses a silica template method with kinetic control of resin polymerization and TEOS hydrolysis, which is scalable. The reaction time modulates pore size, allowing reproducible production of mC with tailored mesopores. The process is compatible with standard chemical engineering practices, though further optimization for large-scale manufacturing is needed.
What are the potential long-term toxicity and biodegradation profiles of the mC nanoparticles?
In vitro biocompatibility tests showed >95% cell viability at 200 μg mL−1, indicating low cytotoxicity. However, long-term in vivo toxicity and biodegradation data are not provided in this study. Carbon-based materials are generally considered biocompatible, but further studies are required to assess chronic exposure and clearance pathways.
How does the combined therapy achieve a 3.7-fold increased cytotoxicity compared to monotherapy, and what is the underlying mechanism?
The combined therapy integrates immediate cytotoxic effects of photothermal treatment with prolonged efficacy of sustained drug release. NIR-triggered hyperthermia enhances tumor permeability, facilitating deeper drug penetration, while pH-responsive release ensures sustained drug exposure. This synergistic effect leads to a 95% reduction in tumor cell viability, significantly outperforming individual treatments.
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