Biodegradable Polymer Nanoparticles for Photodynamic Therapy by Bioluminescence Resonance Energy Transfer

Abstract

Conventional photodynamic therapy is severely constrained by the limited light-penetration depth in tissue. Here, we show efficient photodynamic therapy (PDT) mediated by bioluminescence resonance energy transfer (BRET) that overcomes the light-penetration limitation. The photosensitizer Rose Bengal (RB) was loaded in biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles, which were then conjugated with firefly luciferase. Spectroscopic characterizations indicated that BRET effectively activated RB to generate reactive oxygen species (ROS). In vitro studies of the cellular cytotoxicity and photodynamic effect indicated that cancer cells were effectively destroyed by BRET-PDT treatment. In vivo studies in a tumor-bearing mouse model demonstrated that tumor growth was significantly inhibited by BRET-PDT in the absence of external light irradiation. The BRET-mediated phototherapy provides a promising approach to overcome the light-penetration limitation in photodynamic treatment of deep-seated tumors.

Photodynamic Therapy of Cancers With Internal Light Sources: Chemiluminescence, Bioluminescence, and Cerenkov Radiation

“…Furthermore, this BL-PDT can also suppress distant organ metastasis. Recently, Yang et al ( 2018 ) reported a new BL-PDT system based on the polymer nanoparticle which was assembled from poly(lactic acid) and poly(lactic- co -glycolic acid) and was loaded with Rose Bengal and luciferase. In vitro photodynamic studies showed that this BL-PDT treatment can lead to significant toxicity toward cancer cells.…”

In Vivo Biosensing Using Resonance Energy Transfer

“…Finally, BRET-based photoinduction has potential for therapeutic use as well, as demonstrated by Yang et al [157]. The authors demonstrated efficient photodynamic therapy (PDT) using BRET-based localized excitation to inhibit tumor growth in a mouse model.…”

“…Excised tumors from the five groups visually show the successful tumor growth inhibition by PDT for the PLGA-RB with external light excitation and PLGA-RB with BRET (Figure 13D). PDT using BRET is an interesting way to impact tumor cells in deep tissues, where external light sources struggle to penetrate [157].…”

“…( D ) Excised tumors from the five treated groups on day 14. Reprinted with permission from [157]. Copyright 2018, American Chemical Society.…”

Chemiluminescence-initiated and in situ-enhanced photoisomerization for tissue-depth-independent photo-controlled drug release

“…Recently, the use of near-infrared light with longer wavelength (650–1000 nm) through upconversion, such as two-photon,4,5 upconverting nanoparticles,2 and triplet–triplet annihilation,9 is proposed to improve tissue penetration, but it only increases to millimetre depths. Self-luminescence, including chemiluminescence (CL),10–23 bioluminescence,24–27 and Cerenkov radiation,28 are now deemed to have more potential as tissue-penetration-depth-independent light and has been successfully applied in the highly sensitive bioimaging field 8. However, self-luminescence-driven photoisomerization in vivo remains extremely challenging because such a low-intensity light source insufficiently implements a good photoisomerization effect 8.…”