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Updated: Jun 2, 2026
09:08
Rapid Optimization of a Light-Inducible System to Control Mammalian Gene Expression
Published on: November 4, 2025
An All-in-One Photothermal Nanocomposite Hydrogel for Controlling Inducible Transgene Expression.
Rodrigo Serrano-Yamba1,2,3, Clara Escudero-Duch1,2, Cristina Yus4,5,6
1Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, Madrid 28046, Spain.
ACS Applied Materials & Interfaces
|June 1, 2026
Summary
This study presents a novel implantable hydrogel that uses near-infrared light to control gene expression via localized rapamycin delivery, minimizing systemic toxicity. This innovative approach enables precise, on-demand therapeutic protein production for advanced gene therapies.
Area of Science:
- Biotechnology
- Materials Science
- Gene Therapy
Background:
- Rapamycin is a potent transcriptional inducer for controlled gene expression but causes systemic toxicity.
- Conventional rapamycin administration leads to immunosuppression and off-target effects, limiting its therapeutic use.
- Localized delivery systems are needed to harness rapamycin's benefits while mitigating its drawbacks.
Purpose of the Study:
- To develop a remotely activated, implantable hydrogel system for controlled transgene expression using localized rapamycin.
- To decouple the therapeutic efficacy of rapamycin from its systemic toxicity through nanoparticle encapsulation and targeted delivery.
- To create a safe and customizable platform for site-specific, transgenic protein therapies.
Main Methods:
- Developed poly(lactic-co-glycolic acid) (PLGA) nanoparticles to encapsulate rapamycin for enhanced stability and localized delivery.
- Engineered cells with a dual heat- and dimerizer-responsive gene switch.
- Created photothermal hydrogels incorporating hollow gold nanoparticles and rapamycin-loaded PLGA nanoparticles within a fibrin matrix.
- Utilized near-infrared (NIR) irradiation for remote activation of transgene expression in vivo in mice.
Main Results:
- Nanoencapsulation preserved rapamycin activity, enabling superior long-term dimerizer function compared to the free drug.
- NIR irradiation of implanted hydrogels induced transgene expression comparable to systemic rapamycin, with negligible circulating drug levels.
- Localized rapamycin release modulated macrophage phenotypes (M2 to M1) and promoted scaffold degradation product clearance.
- NIR-triggered hydrogels with VEGF165-producing cells induced a significant angiogenic cascade, increasing microvascular density.
Conclusions:
- Demonstrated a light-triggered, rapamycin-dependent platform for controlled transgene expression.
- Validated the potential of nanoparticle-mediated localized drug delivery to minimize systemic toxicity.
- Showcased the system's capability for site-specific therapeutic protein production, including angiogenic factors.
- Established a customizable and safe tool for advancing next-generation transgenic protein therapies.
