Development of a functionalized UV-emitting nanocomposite for the treatment of cancer using indirect photodynamic therapy

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.Electronic supplementary materialThe online version of this article (10.1186/s12951-018-0344-3) contains supplementary material, which is available to authorized users.

Inorganic Nanoparticles Applied for Active Targeted Photodynamic Therapy of Breast Cancer

“…Studies by Sengar et al (2018) investigated X-PDT for the deep penetration of BC tumors [126]. They synthesized Y2.99Pr0.01Al5O12-based (YP) mesoporous silica (MS) coated NPs and functionalized them with PpIX and FA (YPMS@PpIX@FA) for the X-PDT treatment of BC cells with overexpressed folate receptors (Folr 1) [126].…”

“…Studies by Sengar et al (2018) investigated X-PDT for the deep penetration of BC tumors [126]. They synthesized Y2.99Pr0.01Al5O12-based (YP) mesoporous silica (MS) coated NPs and functionalized them with PpIX and FA (YPMS@PpIX@FA) for the X-PDT treatment of BC cells with overexpressed folate receptors (Folr 1) [126]. The utilized BC in vitro cell lines were PyMT-R221A mouse BC cells (which have high levels of folate receptors), as well as 4T1 BC cells (which have low folate expression) [126].…”

“…They synthesized Y2.99Pr0.01Al5O12-based (YP) mesoporous silica (MS) coated NPs and functionalized them with PpIX and FA (YPMS@PpIX@FA) for the X-PDT treatment of BC cells with overexpressed folate receptors (Folr 1) [126]. The utilized BC in vitro cell lines were PyMT-R221A mouse BC cells (which have high levels of folate receptors), as well as 4T1 BC cells (which have low folate expression) [126]. PyMT-R221A mouse BC cells reported higher cellular uptake of YPMS@PpIX@FA when compared to 4T1 BC cells, revealing that FA targeting of this nanoconjugate was functional [126].…”

“…The utilized BC in vitro cell lines were PyMT-R221A mouse BC cells (which have high levels of folate receptors), as well as 4T1 BC cells (which have low folate expression) [126]. PyMT-R221A mouse BC cells reported higher cellular uptake of YPMS@PpIX@FA when compared to 4T1 BC cells, revealing that FA targeting of this nanoconjugate was functional [126]. Additionally, nonactivated YPMS@PpIX@FA reported a low cytotoxicity when used at concentrations below 25 µg/ml, while upon light activation at 365 nm, a remarkable decrease in PyMT-R221A mouse BC cells was observed [126].…”

SERS imaging elucidates the folate receptor-mediated photothermal/photodynamic synergistic anticancer nanodrugs-induced cell apoptosis

“…However, the traditional PDT treatment suffers from several drawbacks such as high oxygen dependent, poor water solubility and poor targeting of photosensitizer. Moreover, the generated ROS has very short half-life and limited diffusion distance, so the efficiency of PDT is greatly restricted [42,43]. Due to the advantages in easy modification, strong photodynamic effect, cellular respiration promotion, PpIX is becoming a better candidate of photosensitizer [44,45].…”