Heavy-metal free near infrared photoredox catalysts in cancer phototherapy

癌症光疗中不含重金属的近红外光氧化还原催化剂

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Abstract

Herein, five new far red/near infra-red (NIR) heavy-metal free photosensitizers (PSs) were developed by donor modulation of the planar perylenimide (PI) core, exhibiting large Stokes shifts of 213-270 nm. The dimethyl-enabled aggregation-induced enhanced emission (AIEE) and tunable AIEE/AIE behaviors of the RPI PSs aided precise and efficient superoxide (O(2)˙(-)) generation for cancer phototherapy, viz.R = Ph (PhPI), PhNH(2) (ANPI), PhN(CH(3))(2) (DMPI), -PhN(Ph)(2) (TPPI), PhN(BiPh)(2) (BPPI) to obtain distinct NIR emitters and NIR photoredox catalytic properties. Notably, the solid state NIR emissive DMPI, TPPI and BPPI showed far-red/NIR AIEE, AIE and AIEE behaviors in aqueous media, whereas PhPI and ANPI displayed aggregation-caused quenching (ACQ) effects. A key discovery is the dimethyl-induced transformation of ACQ-to-AIEE in DMPI, enabling a very rare and unusual feature of inducing NIR AIEE properties in the PS. Moreover, the ACQ molecules PhPI and ANPI generate O(2)˙(-)/˙OH (type-I PS/photoredox) efficiently, DMPI exhibits NIR AIEE photoredox characteristics for O(2)˙(-) (type-I PS) generation, TPPI illustrates far-red AIE photoredox/type-II PS for O(2)˙(-/1)O(2) (singlet oxygen quantum yield, Φ (Δ) = 0.59 in aqueous media), while BPPI demonstrated far-red AIEE photoredox for O(2)˙(-) in cancer cells. These systems highlight the diverse optical and therapeutic properties obtained by carefully varying the donor moiety in the RPIs. The most prominent dimethyl-induced NIR AIEE design strategy in DMPI reveals an exceptional heavy metal-free (NIR AIEE/NIR) photoredox catalyst PS, offering precise and efficient electron transfer for O(2)˙(-) production. Importantly, the NIR photoredox catalysts are rarely reported, and the introduction of NIR AIEE photoredox sensitizers expands the scope of current photoredox research. The photocatalytic superoxide generator TPPI, developed via triplet-ground-state splitting energy modulation, induces significant cancer cell death through a partial O(2)-recycling pathway involving Haber-Weiss/Fenton reactions.

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