Chemiluminescence resonance energy transfer–based nanoparticles for quantum yield–enhanced cancer phototheranostics

Abstract

Chemiluminescence (CL) has recently gained attention for CL resonance energy transfer (CRET)–mediated photodynamic therapy of cancer. However, the short duration of the CL signal and low quantum yield of the photosensitizer have limited its translational applications. Here, we report CRET-based nanoparticles (CRET-NPs) to achieve quantum yield–enhanced cancer phototheranostics by reinterpreting the hidden nature of CRET. Owing to reactive oxygen species (ROS)–responsive CO2 generation, CRET-NPs were capable of generating a strong and long-lasting photoacoustic signal in the tumor tissue via thermal expansion–induced vaporization. In addition, the CRET phenomenon of the NPs enhanced ROS quantum yield of photosensitizer through both electron transfer for an oxygen-independent type I photochemical reaction and self-illumination for an oxygen-dependent type II photochemical reaction. Consequently, owing to their high ROS quantum yield, CRET-NPs effectively inhibited tumor growth with complete tumor growth inhibition in 60% of cases, even with a single treatment.

Chemiluminescence Resonance Energy Transfer Efficiency and Donor–Acceptor Distance: from Qualitative to Quantitative

“…[3][4][5] In comparison to FRET,C RET offers several inherent advantages,i ncluding elimination of external photoexcitation, absence of autofluorescence and photobleaching,a nd thus it could provide excellent performances in immunoassays,m acromolecular analysis,small molecule detection, bioimaging,and therapeutic applications. [6][7][8][9][10][11][12][13][14][15][16] Unfortunately,t here is no experimental evidence to support the statement that CRET efficiencyi s proportional to the inverse sixth power of the donor-acceptor distance.A ccordingly,C RET is limited to be qualitative, rather than quantitative.Such agap would greatly limit the indepth understanding and multidisciplinary applications of CRET.T herefore,i ti se ssential to pursue af easible strategy to measure the quantitative relationship between CRET efficiency and donor-acceptor distance.…”

Photodynamic therapy: A next alternative treatment strategy for hepatocellular carcinoma?

“…The use of a self-illuminating system as a light source provides an intriguing solution to the light penetration issues of conventional PDT[ 110 ]. Some self-illuminating systems, including chemiluminescence[ 111 ] and bioluminescence[ 112 ], are promising candidates as internal light sources for PDT. These self-illuminators are small in size (ranging from the atomic/molecular to the nanometer scale) and thus can be delivered to any pathological tissue[ 113 ].…”

Highly efficient, all-organic bioluminescence-photosensitizer conjugate eradicates early-stage tumors and prevents metastasis in mice

“…Although the molecular luminescence has much weaker intensity than what external irradiation can provide, efficient Förster resonance energy transfer from the luminescent group to photosensitizers can, in principle, compensate for the intensity difference and produce substantial PDT effects. Recently, a combination of a chemiluminescent donor, luminol, and a photosensitizer as the acceptor was shown to produce efficient ROS-induced cell death in vitro and tumor growth inhibition in vivo [9][10] . However, luminol requires endogenous H2O2 at a high concentration in the target tissue.…”