New nanoparticles allow synergy of radiotherapies and photodynamic therapies of deep tumor tissues

Researchers Dr. Yansong Feng and Prof. Hong Zhang from the Van ‘t Hoff Institute for Molecular Sciences of the University of Amsterdam (UvA) have designed and synthesized new multifunctional multilayered nanoparticles that enable a combination of radiotherapy and photodynamic therapy for deep cancerous tissue. A first preclinical evaluation of the particles demonstrated their therapeutic potential. A patent is pending and the university is now seeking partners for further development or licensing.

The originality of nanoparticles is that they make it possible to combine radiotherapy and photodynamic therapy using only X-rays. The particles also facilitate deep tissue imaging, allowing image-guided targeting of combined therapy.

Combination therapy

In photodynamic therapy, visible light is used to activate photosensitizers which release radical oxygen species to destroy cancer cells. It attacks different parts of a cancer cell compared to conventional radiation therapy using X-rays. Using the two therapies together enhances the destruction of tumor tissue and often reduces the dose of X-rays required. However, because photodynamic therapy is triggered by light, it is difficult to use it to treat cancerous tissue deep inside the body. This requires an invasive procedure such as endoscopy using a fiber optic. With X-rays, this problem does not exist. They easily enter the body and are concentrated in such a way that they can do their devastating work at the tumor site.

By designing nanoparticles capable of emitting visible light when irradiated with X-rays, UvA researchers have now found a way to apply photodynamic therapy to deep places without invasive procedures. The particles were developed during doctoral research by Dr Yansong Feng, supervised by Professor Hong Zhang of UvA’s Molecular Photonics Research Group.

Image guided targeting

The nanoparticle consists of a core surrounded by two outer layers. The outermost layer is capable of scintillation – a process that converts X-rays into visible light and thus enables photodynamic therapy at any location accessible by radiation therapy. The second layer is a buffer layer which energetically isolates the scintillating layer from the core of the nanoparticles. Within the core itself, the researchers implemented another important therapy-enhancing feature. He is able to upconversion luminescence meaning it can change the frequency of light. The researchers tuned the upconversion so that the nanoparticle would emit red visible light upon illumination with near-infrared (NIR) radiation or X-rays. In this way, they effectively created the possibility of a image-guided therapy. Upon illumination with NIR, which has a relatively long penetration depth, the particles light up in an intense red color and thus reveal the location of the tumor. The nucleus continues to emit red light during radiation therapy using X-rays, although at a lower intensity. The red light emitted does not interfere with photodynamic therapy.

Positive preclinical evaluation

As a proof of principle, the researchers studied the performance of nanoparticles in cancer treatment studies with cell cultures (in vitro) and mice (live). This provided a clear indication of the particles’ safety and therapeutic potential.

In cooperation with Innovation Exchange Amsterdam (IXA, the university’s technology transfer office), the researchers are now looking for licensees and/or partners to further develop this new approach into a commercially viable application, which would include carrying out preclinical trials and further entry into full clinical trials. This would help establish the safety of nanoparticles, their ease of use, their performance during treatment and the overall effectiveness of their application.

Source:

University of Amsterdam (UVA)

Journal reference:

Yansong Feng, Xiaomeng Liu, Qiqing Li, Shilin Mei, Kefan Wu, Jun Yuan, Langping Tu, Ivo Que, Filippo Tamburini, Fabio Baldazzi, Alan Chan, Luis J. Cruz, Jing Zuo, Changjiang Yao and Hong Zhang: Glittering Nanoplatform with Upconversion function for the synergy of radiation and photodynamic therapies of deep tumors Journal of Materials Chemistry C 10 (2022) 688-695. DOI: 10.1039D1TC04930E

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