Molecular Design of Conjugated Small Molecule Nanoparticles for Synergistically Enhanced PTT/PDT

Simultaneous photothermal therapy(PTT)and photodynamic therapy(PDT)is beneficial for enhanced cancer therapy due to the synergistic effect.Conventional materials developed for synergistic PTT/PDT are generally multicomponent agents that need complicated preparation procedures and be activated by multiple laser sources.The emerging monocomponent diketopyrrolopyrrole(DPP)-based conjugated small molecular agents enable dual PTT/PDT under a single laser irradiation,but suffer from low singlet oxygen quantum yield,which severely restricts the therapeutic efficacy.Herein,we report acceptor-oriented molecular design of a donor-acceptor-donor(D-A-D)conjugated small molecule(IID-ThTPA)-based phototheranostic agent,with isoindigo(IID)as selective acceptor and triphenylamine(TPA)as donor.The strong D-A strength and narrow singlet-triplet energy gap endow IID-ThTPA nanoparticles(IID-ThTPA NPs)high mass extinction coefficient(18.2 L g^-1 cm^-1),competitive photothermal conversion efficiency(35.4%),and a dramatically enhanced singlet oxygen quantum yield(84.0%)comparing with previously reported monocomponent PTT/PDT agents.Such a high PTT/PDT performance of IID-ThTPA NPs achieved superior tumor cooperative eradicating capability in vitro and in vivo.

Small molecule conjugates with selective estrogen receptor β agonism promote anti-aging benefits in metabolism and skin recovery

Estrogen is imperative to mammalian reproductivity,metabolism,and aging.However,the hormone activating estrogen receptor(ERs)αcan cause major safety concerns due to the enrichment of ERαin female tissues and certain malignancies.In contrast,ERβis more broadly expressed in metabolic tissues and the skin.Thus,it is desirable to generate selective ERβagonist conjugates for maximizing the therapeutic effects of ERs while minimizing the risks of ERαactivation.Here,we report the design and production of small molecule conjugates containing selective non-steroid ERβagonists Gtx878 or genistein.Treatment of aged mice with our synthesized conjugates improved aging-associated declines in insulin sensitivity,visceral adipose integrity,skeletal muscle function,and skin health,with validation in vitro.We further uncovered the benefits of ERβconjugates in the skin using two inducible skin injury mouse models,showing increased skin basal cell proliferation,epidermal thickness,and wound healing.Therefore,our ERβ-selective agonist conjugates offer novel therapeutic potential to improve aging-associated conditions and aid in rejuvenating skin health.