Mesoporous Silica-Coated Upconversion Nanoparticles Assisted Photodynamic Therapy Using 5-Aminolevulinic Acid: Mechanistic andIn VivoStudies

Abstract

Exclusively red-emitting upconversion nanoparticles (UCNPs) with the composition NaErF4:0.5%Tm as a core and NaYF4 as a shell were synthesized for performing photodynamic therapy (PDT). A possible mechanism was proposed for core–shell UCNPs formation. For loading a maximum amount of 5-aminolevulinic acid (5-ALA), mesoporous silica coating was performed on UCNPs. Studies under dark conditions confirmed the biocompatibility of 5-ALA-loaded UCNPs formulation (UCNPs-5-ALA) with MCF-7 cells. Meanwhile, studies under light-exposed conditions exhibited effective cytotoxicity against MCF-7 cells. Studies employing D2O-based cell cultured media and addition of DABCO in cell culture established that the cell death was due to oxidation of cellular components by reactive oxygen species (ROS) triggering the apoptosis. The formation of ROS was confirmed by DCF­(H)­DA-based ROS analysis via fluorescence microscopy to demonstrate the ROS production, which mediates the programmed cell death. Additionally, we have validated the apoptosis in MCF-7 cells with flow cytometry analyses. This was further confirmed by an electrophoretic mobility shift assay on nuclear extract and measurement of mitochondrial membrane potential. In the case of animal model studies, the formulation UCNPs-5-ALA without irradiation (980 nm) did not possess any in vivo cytotoxicity on tumor-induced SCID mice and there was a minimum migration of UCNPs-5-ALA to the vital organs but maximum retention at the tumor site only. Meanwhile, only the mice treated with UCNPs-5-ALA and irradiated on the tumor region with 980 nm laser (500 mW) for 20 min possessed a tumor with a size reduced to about 75% as compared with the corresponding control groups. To the best of our knowledge, this type of study was conducted for the first time employing exclusively red-emitting phosphors for effective PDT.

Dominant red upconversion emission in LiErF4-based nanoparticles by reducing spontaneous emission of Yb3+

“…It can be clearly seen that green and red emission peaks appear at 550 and 668 nm, which correspond to the 4 S 3/2 → 4 I 15/2 and 4 F 9/2 → 4 I 15/2 transitions of Er 3+ . 35,36 Furthermore, NIR-I emission at 797 nm can be observed under 1532 nm excitation, which is attributed to the 3 H 4 → 3 H 6 transition of Tm 3+ . As the concentration of Yb 3+ increases, the UC emission intensity shows a trend of first increasing and then decreasing.…”

Lanthanide-Doped Upconversion Nanoparticles: Exploring A Treasure Trove of NIR-Mediated Emerging Applications

“…Over the past decade, much progress has been made in the synthesis and surface engineering of UCNPs to allow for biomedical and other specialized applications. − Some of the leading advances in the fundamental surface chemistry of UCNPs have been discussed in detail by Gorris and co-workers . While some key challenges to the field remain, as highlighted by Wilhelm and co-workers, UCNP-based research have also advanced well into new and innovative areas by virtue of the unique spectroscopic properties of these materials .…”

“…Other related applications of UCNPs in photocatalysis and cancer therapeutics have also been detailed by Zhang and co-workers . UCNPs have thus been well-exploited for in vitro (as nanosensors for biomarkers) and in vivo applications (as luminescent tags for bioimaging). ,− While many of these traditional applications of upconversion, such as theranostics and analytical probe design, have exploited key advantages of UCNPs, other new areas remain underexplored.…”

Nanotechnology and photodynamic therapy from a clinical perspective

“…Summary of some of the reported studies in 2022 on the use of NP-based PS for PDT enhancement NaErF 4 :0.5%Tm and shell of NaYF 4) coated with MSN and loaded with 5-ALA Cancer treatment[10] …”