A multi-parameter-induced activation of gas therapeutic platform to remarkably amplify photodynamic therapy efficacy

Gas therapy(GT)combined with photodynamic therapy(PDT)is an effective strategy to compensate for the PDT limitation caused by the hypoxic tumor microenvironment,which can greatly improve PDT efficacy.The uncontrolled leakage of gas molecules during delivery seriously hinders its practical biological application.Herein,we report a multifunction nanomedicine that enables precise gas therapy(including carbon monoxide(CO)release and H_(2)S depletion)using a multi-parameter-induced activation gas release strategy,enlarging the PDT efficacy.This nanomedicine uses a disulfide bond to covalently link a photosensitizer with the CO donor 3-hydroxyflavone(3-HF).The disulfide bond can be specifically consumed in H_(2)S-rich tumor areas,releasing the CO donor(3-HF),and also depleting H_(2)S.More importantly,the photo-controlled production of^(1)O_(2)can induce 3-HF precise release of CO in the tumor location.Such H_(2)S,light,and^(1)O_(2)multi-parameter-induced activation of gas release strategy ensures the accuracy of GT to amplify PDT efficiency.As expected,in vitro and in vivo investigations show that GT makes up for the PDT limitation,exhibiting the highest tumor therapeutic effect.This multi-parameter-activated design strategy provides a new way to improve the precision and efficacy of multimodal synergistic therapy of tumors.

A biomimetic and bioactive scaffold with intelligently pulsatile teriparatide delivery for local and systemic osteoporosis regeneration

Osteoporosis is one of the most disabling consequences of aging,osteoporotic fractures and higher risk of the subsequent fractures leading to substantial disability and deaths,indicating both local fractures healing and the early anti-osteoporosis therapy are of great significance.Teriparatide is strong bone formation promoter effective in treating osteoporosis,while side effects limit clinical applications.Traditional drug delivery is lack of sensitive and short-term release,finding a new non-invasive and easily controllable drug delivery to not only repair the local fractures but also improve total bone mass has remained a great challenge.Thus,bioinspired by the natural bone components,we develop appropriate interactions between inorganic biological scaffolds and organic drug molecules,achieving both loaded with the teriparatide in the scaffold and capable of releasing on demand.Herein,biomimetic bone microstructure of mesoporous bioglass,a near-infrared ray triggered switch,thermosensitive liposomes based on a valve,and polydopamine coated as a heater is developed rationally for osteoporotic bone regeneration.Teriparatide is pulsatile released from intelligent delivery,not only rejuvenating osteoporotic bone defect,but also presenting strong systemic anti-osteoporosis therapy.This biomimetic bone carrying novel drug delivery platform is well worth expecting to be a new promising strategy and clinically commercialized to help patients survive from the osteoporotic fracture.