Protoporphyrin IX and IR-820 fluorophore–encapsulated organically modified silica nanoparticles

Protoporphyrin IX (PpIX) and IR-820 fluorophore–encapsulated organically modified silica nanoparticles (ORMOSIL NPs), abbreviated as PpIX/IR-820–doped ORMOSIL NPs, were synthesized by Qian et al. for two-photon photodynamic therapy (PDT) and optical imaging (1). PDT has been investigated for several decades as an alternative to chemotherapy and radiotherapy for tumor treatment (2, 3). PDT involves the use of light, a photosensitizer (PS), and tissue oxygen. Under light excitation, PS transfers its energy to neighboring oxygen molecules, resulting in the generation of singlet oxygen (O) and other cytotoxic reactive oxygen species, which leads to apoptosis and necrosis of cancer cells. To date, most PSs developed for PDT are hydrophobic, aggregate easily in blood, and exhibit poor tumor selectivity (1, 2). One technique to overcome these issues is to link PSs to or encapsulate them in nanocarriers (4, 5). Nanocarriers have been synthesized with diverse nanomaterials such as polymers, metals, semi-conductors, and silica. ORMOSIL NPs have shown great potential as an ideal nano-platform for theranostic applications because of their unique properties (6-8). First, ORMOSIL NPs are chemically inert, and the silica matrix porosity is resistant to swelling or changes in varying pH conditions. Second, ORMOSIL NPs can be loaded with both hydrophilic and hydrophobic payloads and protected from degradation by the bio-environment. PSs can be encapsulated in the monomeric form without loss of activity. Third, ORMOSIL NPs are mesoporous, which allows controlled release of the encapsulated biomolecules. Fourth, ORMOSIL NPs are able to accumulate selectively in tumors through the enhanced permeability and retention effects of tumor tissues. Finally, the size, shape, porosity, and monodispersibility of the ORMOSIL NPs can be controlled during preparation, and their surfaces can be functionalized with various chemical groups and/or targeting biomolecules. The most recent studies on PDT with ORMOSIL NPs have focused on the targeted delivery for two-photon PDT in deep tissues and on the multimodal applications within one NP platform, such as the combination of magnetic resonance imaging, optical imaging, and PDT (2, 3). For imaging and therapeutic purposes, Qian et al. synthesized PpIX-doped and near-infrared (NIR) dye IR-820–doped ORMOSIL NPs (1). PpIX is a photosensitizer currently used in the clinic. The investigators tested the feasibility of using the NPs for optical imaging and PDT of tumor cells under two-photon excitation (1).