Second harmonic generation nanoparticles enables Near-Infrared Photodynamic Therapy from visible light reactive photosensitizer conjugates

Abstract

Combination of photosensitizers (PS) with nanotechnology can improve the therapeutic efficiency of clinical Photodynamic Therapy (PDT) by converting visible light reactive PSs into Near-Infrared (NIR) light responsive molecules using Harmonic Nanoparticles (HNP). To test the PDT efficiency of HNP-PS conjugates, pathogenic S. aureus cell cultures were treated with perovskite (Barium Titanate) Second Harmonic Generation (SHG) nanoparticles conjugated to photosensitizers (PS) (we compared both FDA approved Protoporphyrin IX and Curcumin) and subjected to a femtosecond pulsed Near-Infrared (NIR) laser (800 nm, 232–228 mW, 12–15 fs pulse width at repetition rate of 76.9 MHz) for 10 minutes each. NIR PDT using Barium Titanate (BT) conjugated with Protoporphyrin IX as HNP-PS conjugate reduced the viability of S. aureus cells by 77.3 ± 9.7% while BT conjugated with Curcumin did not elicit any significant effect. Conventional PSs reactive only to visible spectrum light coupled with SHG nanoparticles enables the use of higher tissue penetrating NIR light to generate an efficient photodynamic effect, thereby overcoming low light penetration and tissue specificity of conventional visible light PDT treatments.

Phyto-Photodynamic Therapy of Prostate Cancer Cells Mediated by Yemenite ‘Etrog’ Leave Extracts

“…Finally, the PDT treatment was therefore conducted at a concentration that was compatible with a shorter incubation time (10.93 mg/mL). Producing ROS within the malignant cellular environment may increase the probability of apoptosis pathway stimulation through DNA fragmentation, mitochondrial membrane damage, Golgi damage, etc., resulting in desired tumor cell destruction and death [ 29 , 30 , 31 , 32 , 33 , 34 ]. The findings of maximum working concentration (10.93 mg/mL) and minimum pre-treatment incubation period (1 h) were essential to perform phyto-FDT treatment.…”

“…In detail, the type I pathway reaction involves electron transfer from the excited singlet or triplet states of PS to O 2 , leading to the generation of ROS such as: OH*, H 2 O 2 , and O 2 − ( Figure 1 ). The type II pathway reaction occurs via direct energy transfer between the excited triplet state PS (resulting from singlet excited state intersystem crossing), having electrons with parallel spins acting as radicals, and the triplet ground state oxygen molecule, resulting in highly reactive singlet oxygen ( 1 O 2 ) production ( Figure 1 ) [ 1 , 4 , 13 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. The electrons in the first excited singlet state also have numerous pathways to release the absorbed energy back to their ground state, either by emitting light (fluorescence) or by releasing heat (internal conversion).…”

“…Most of the chemically synthesized photosensitizers, such as rose Bengal, methylene blue, toluidine blue, squaraine dyes, and others, lack widespread approval for medical use due to safety concerns [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. Therefore, phyto-photosensitizer mediators are becoming a serious alternative.…”

Advances in NIR-Responsive Natural Macromolecular Hydrogel Assembly Drugs for Cancer Treatment

“…The AuNRs in the hydrogel were heated using NIR light, resulting in the destruction of the hydrogel network and the release of a large amount of drug. In addition, ICG can also be encapsulated into microgel particles by microfluidic technology, and this has effective PTT/PDT performance under NIR light [ 144 , 145 ].…”