Abstract
BackgroundPhotodynamic therapy is a promising cancer therapy modality but its application for deep-seated tumor is mainly hindered by the shallow penetration of visible light. X-ray-mediated photodynamic therapy (PDT) has gained a major attention owing to the limitless penetration of X-rays. However, substantial outcomes have still not been achieved due to the low luminescence efficiency of scintillating nanoparticles and weak energy transfer to the photosensitizer. The present work describes the development of Y2.99Pr0.01Al5O12-based (YP) mesoporous silica coated nanoparticles, multifunctionalized with protoporphyrin IX (PpIX) and folic acid (YPMS@PpIX@FA) for potential application in targeted deep PDT.ResultsA YP nanophosphor core was synthesized using the sol–gel method to be used as X-ray energy transducer and was then covered with a mesoporous silica layer. The luminescence analysis indicated a good spectral overlap between the PpIX and nanoscintillator at the Soret as well as Q-band region. The comparison of the emission spectra with or without PpIX showed signs of energy transfer, a prerequisite for deep PDT. In vitro studies showed the preferential uptake of the nanocomposite in cancer cells expressing the folate receptorFolr1, validating the targeting efficiency. Direct activation of conjugated PpIX with UVA in vitro induced ROS production causing breast and prostate cancer cell death indicating that the PpIX retained its activity after conjugation to the nanocomposite. The in vivo toxicity analysis showed the good biocompatibility and non-immunogenic response of YPMS@PpIX@FA.ConclusionOur results indicate that YPMS@PpIX@FA nanocomposites are promising candidates for X-ray-mediated PDT of deep-seated tumors. The design of these nanoparticles allows the functionalization with exchangeable targeting ligands thus offering versatility, in order to target various cancer cells, expressing different molecular targets on their surface.
Highlights
Photodynamic therapy is a promising cancer therapy modality but its application for deep-seated tumor is mainly hindered by the shallow penetration of visible light
Y 2.99Pr0.01Al5O12 (YP) was selected based on its radioluminescence emission properties in the 300–450 nm range, which is critical for the activation of the photosensitizer protoporphyrin IX (PpIX)
A mesoporous silica shell (MS) was coated on the surface of the YP core, which was confirmed by transmission electron microscopy (TEM) (Fig. 1a and Additional file 1: Figure S1a)
Summary
Photodynamic therapy is a promising cancer therapy modality but its application for deep-seated tumor is mainly hindered by the shallow penetration of visible light. Various inorganic nanoparticles including quantum dots, gold nanoparticles [8, 9] and upconversion nanoparticles [10, 11], with a high extinction coefficient in NIR region are used to improve the therapeutic efficiency or alternatively, the light is delivered to deep cancerous tissues via optical fibers [7]. With these strategies, tissue penetration depth is achieved to some extent, new approaches are still required for treating deep-seated tumors with greater efficiency and throughout the body when cancer has metastasized. Most of the clinically approved PS’s weakly absorb direct X-ray photons and a system is needed in order to convert the X-ray into photons that can activate the PS
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