ALP-Activated Chemiluminescence PDT Nano-Platform for Liver Cancer-Specific Theranostics

Abstract

Photodynamic therapy (PDT) is a promising therapeutic approach that has been extensively applied in curing cancers. However, the limited penetration depth of external light makes PDT only practical for some superficial tumor treatments. Moreover, an external light irradiation might cause damages to adjacent normal tissues. Additionally, the poor targeting ability of PDT can lead to side effects like skin phototoxicity. Therefore, a PDT strategy addressing these drawbacks is urgently exploited. Herein, we constructed a chemiluminescence theranostics platform named MSN@H6L@β-CD@AMPPD NPs for liver cancer-specific, in situ diagnosis and therapy without an external light source. Through the interaction of host–guest, 3-[(2-spiroadamatane)-4-methoxy-4-(3-phosphoryloxy)-phenyl-1,2-dioxetane] dioxetane, a chemiluminescence substrate of the liver cancer biomarker alkaline phosphatase was integrated with β-cyclodextrin. Then, the β-cyclodextrin was covalently bound to the mesoporous silica loaded with (4-carboxyphenyl) porphyrin to finally obtain the MSN@H6L@β-CD@AMPPD NPs. These NPs can be specifically hydrolyzed by the liver cancer alkaline phosphatase and lead to the liver cancer-targeting chemiluminescence. Subsequently, (4-carboxyphenyl) porphyrin was excited by the chemiluminescence through chemiluminescence resonance energy transfer and created both near-infrared fluorescence and 1O2. This strategy greatly promotes the penetration depth and targeting ability of the PDT. In brief, the platform accomplishes a PDT nano-theranostics for liver cancer and provides a method for the imaging, diagnosis, and therapy of tumors in deep tissue.

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

“…As shown in Figure 2 d, the CL spectrum of luminol was recorded in the presence of 5 mM of H 2 O 2 and 10 μM of Co 2+ , which could overlap with the absorption spectra of the micelle solutions of C 8 ‐TPE‐C 4 TAB, C 4 ‐TPE‐C 8 TAB, and TPE‐C 12 TAB [2, 16] . It was worth noting that high CRET efficiency can still be obtained by shortening the donor–acceptor distance in the presence of the small overlap between the emission of donor and the absorption of acceptor [27–29] . Therefore, C 8 ‐TPE‐C 4 TAB, C 4 ‐TPE‐C 8 TAB, and TPE‐C 12 TAB could act as the high‐performance CRET acceptors in the micelles.…”

“…The fluorescence quantum yields of the three micelle solutions (80 μM) were 8.45 %, 15.19 %, and 9.10 %, indicating that the TPE groups could intensely emit in the micelles. In addition, the spectral overlap between donor emission and acceptor absorption was essential for RET to occur [27–29] . As shown in Figure 2 d, the CL spectrum of luminol was recorded in the presence of 5 mM of H 2 O 2 and 10 μM of Co 2+ , which could overlap with the absorption spectra of the micelle solutions of C 8 ‐TPE‐C 4 TAB, C 4 ‐TPE‐C 8 TAB, and TPE‐C 12 TAB [2, 16] .…”

“…[22,24] Thef luorescence quantum yields of the three micelle solutions (80 mM) were 8.45 %, 15.19 %, and 9.10 %, indicating that the TPE groups could intensely emit in the micelles.I na ddition, the spectral overlap between donor emission and acceptor absorption was essential for RET to occur. [27][28][29] As shown in Figure 2d,t he CL spectrum of luminol was recorded in the presence of 5mMo fH 2 O 2 and 10 mMo fC o 2+ ,w hich could overlap with the absorption spectra of the micelle solutions of C 8 -TPE-C 4 TAB, C 4 -TPE-C 8 TAB, and TPE-C 12 TAB. [2,16] It was worth noting that high CRET efficiencyc an still be obtained by shortening the donor-acceptor distance in the presence of the small overlap between the emission of donor and the absorption of acceptor.…”

“…[2,16] It was worth noting that high CRET efficiencyc an still be obtained by shortening the donor-acceptor distance in the presence of the small overlap between the emission of donor and the absorption of acceptor. [27][28][29] Therefore,C 8 -TPE-C 4 TAB, C 4 -TPE-C 8 TAB, and TPE-C 12 TABc ould act as the high-performance CRET acceptors in the micelles.…”

A Microfluidic Chip-Based MRS Immunosensor for Biomarker Detection via Enzyme-Mediated Nanoparticle Assembly

“…Immunoassays have always been irreplaceable methods in disease diagnosis, environmental monitoring, and medical treatment evaluation (Kingsmore, 2006;Rusling et al, 2010;Barbosa and Reis, 2017). Many methods, including gold immunochromatography assay (GICA) Yang et al, 2021), chemiluminescent immunoassay (CLIA) (Iranifam, 2014;Fan et al, 2021), and enzyme-linked immunoassay (ELISA) (Raleigh et al, 1992;Zhang et al, 2019), were designed for tumor marker detection. The above conventional methods have their superiority and have been applied to clinical practice.…”