ALBA Synchrotron
Researchers at the Centro de Investigación Príncipe Felipe have developed a multifunctional nanomaterial that combines tumor imaging and photodynamic therapy to target glioblastoma, a brain cancer with very poor prognosis and limited therapeutic options. Currently at the preclinical stage, the research explores new drug delivery strategies for this hard-to-treat brain tumors. Experiments at the NCD-SWEET beamline of ALBA provided key insights into how the nanomaterial self-assembles and how its structure changes after drug loading, helping researchers optimise its design.
Glioblastoma remains one of the greatest challenges in oncology. The tumor grows rapidly, infiltrates healthy brain tissue and is particularly difficult to treat because the blood-brain barrier prevents many drugs from reaching the brain. In this context, nanomedicine has emerged as a promising approach for developing more precise and less invasive therapies.
Researchers from the Centro de Investigación Príncipe Felipe (CIPF) - led by María Jesús Vicent, responsible of the Therapeutic Polymers Laboratory- have now developed a new multifunctional nanoplatform designed to address several of these challenges simultaneously. It is based on a new generation of polymeric nanocarriers designed to deliver therapeutic compounds while allowing tumor tissue to be visualised in real-time using imaging techniques.
The platform has also been designed to evaluate its combined use with photodynamic therapy, a minimally invasive treatment that uses light to activate photosensitive compounds and destroy cancer cells. The study is currently at the preclinical stage, and its findings are based on experiments carried out in advanced laboratory models.
The modular design also makes the platform adaptable for other diseases requiring multifunctional nanomedicine approaches.
Smart nanocarriers and intranasal delivery
The new nanomaterial consists of star-shaped nanocarriers: polymeric structures built around a zinc-based photosensitive compound structure that strongly absorbs near-infrared light.
So, nanocarriers can be used both to visualise tumors and to enable the photodynamic therapy by selectively destroying cancer cells upon light activation. Experiments showed that the nanoparticles efficiently entered glioblastoma cells and remained active long enough to support both imaging and treatment.
The researchers also incorporated the chemotherapy drug paclitaxel into the platform. Laboratory studies showed that combining chemotherapy with photodynamic therapy produced a stronger anti-tumor effect than the original platform alone.
Another important aspect of the study was the integration of the nanocarriers into a hyaluronic acid-based hydrogel for intranasal administration. The intranasal delivery route provides a non-invasive way to bypass the blood-brain barrier, which blocks most systemically administered drugs from reaching the brain. The obtained results provided valuable insights for the development of future less invasive therapies for brain tumors.
Understanding the nanomaterial with synchrotron light
To understand why the platform behaves the way it does, the researchers investigated its internal structure using Small-Angle X-ray Scattering (SAXS) at the NCD-SWEET beamline of the ALBA Synchrotron. “In contrast to lab-based techniques, synchrotron SAXS, thanks to its high brilliance, offers the unique capacity to probe low-contrast structures and unveil how nanomaterials assemble in solution under conditions that closely mimic their biological surroundings.”, explains Cristián Huck, beamline scientist at NCD-SWEET.
The measurements showed that the nanomaterial spontaneously self-assembles into elongated supramolecular structures in water. They also revealed that attaching paclitaxel subtly changes this internal organisation, reducing interactions between the photoactive components of the platform. These structural changes help explain its improved optical and therapeutic behaviour and provide valuable information for the rational design of future nanomedicines.
According to Dr María Jesús Vicent, "the platform is made up of tailor-made nanocarriers whose structure can be modified to control key properties such as solubility, drug-loading capacity and the way they self-organise in the body. These nanoparticles spontaneously assemble into stable structures capable of penetrating deep into tumor tissue."
“The study also confirmed that the lack of oxygen inside tumors, a common feature of glioblastoma, remains one of the main factors limiting the effectiveness of this type of treatment”, adds Amina Benaicha, PhD researcher at CIPF.
Although the experimental results are promising, the researchers emphasise that further studies in animal models and, subsequently, clinical trials will be required to evaluate the safety and efficacy of this technology before it can be considered for clinical use.
Photoactive Porphyrin core decorated with Polyglutamate arms. This arms could change π-π interactions changing from a fibrilar to a globular structure that change the delivery properties on a selected target.
A collaborative effort
The study involved a broad multi-institutional collaboration across Spain. The work was led by the Centro de Investigación Príncipe Felipe (CIPF). Glioblastoma-on-a-chip experiments were conducted with support from the Universidad de Zaragoza and the Aragón Health Research Institute (IISA), through the Unidad de Apoyo Preclínico de Aragón (UAPA). Biodistribution imaging was carried out at the Biomedical Imaging and Metabolomics Section of the Central Unit for Medical Research (UCIM) at the University of València. Scanning electron microscopy was facilitated by Prof. Beatriu Escuder's group at the Universitat Jaume I (UJI). The A172 cell line was provided by Dr. Julia Lorenzo at the Universitat Autònoma de Barcelona (UAB). The work also received support from the Spanish cancer research association (AECC), CIBERONC, and European funding through the NextGenerationEU program, reflecting a coordinated national and European effort to advance nanomedicine for brain cancer.