De novo design of highly efficient type-Ⅰphotosensitizer based onπ-conjugated oligomer for photodynamic eradication of multidrug-resistant bacterial infections

Traditional photosensitizers show limited singlet oxygen generation in hypoxic infection lesions,which greatly suppress their performance in antibacterial therapy.Meanwhile,there still is lack of feasible design strategy for developing hypoxia-overcoming photosensitizers agents.Herein,radical generation ofπ-conjugated small molecules is efficiently manipulated by an individual selenium(Se)substituent.With this strategy,the first proof-of-concept study of a Se-anchored oligo(thienyl ethynylene)(OT-Se)with high-performance superoxide radical(O_(2)^(·-))and hydroxyl radical(·OH)generation capability is present,and achieves efficient antibacterial activities towards the clinically extracted multidrug-resistant bacteria methicillin-resistant S.aureus(MRSA)and carbapenem-resistant E.coli(CREC)at sub-micromolar concentration under a low white light irradiation(30 mW/cm^(2)).The water-dispersible OT-Se shows a good bacteria-anchoring capability,biocompatibility,and complete elimination of multidrug-resistant bacteria wound infection in vivo.This work offers a strategy to boost type-I photodynamic therapy(PDT)performance for efficient antibacterial treatments,advancing the development of antibacterial agents.

Effect of physicochemical properties on in vivo fate of nanoparticle-based cancer immunotherapies

Current advances of immunotherapy have greatly changed the way of cancer treatment.At the same time,a great number of nanoparticle-based cancer immunotherapies(NBCIs)have also been explored to elicit potent immune responses against tumors.However,few NBCIs are nearly in the clinical trial which is mainly ascribed to a lack understanding of in vivo fate of nanoparticles(NPs)for cancer immunotherapy.NPs for cancer immunotherapy mainly target the immune organs or immune cells to enable effcient antitumor immune responses.The physicochemical properties of NPs including size,shape,elasticity and surface properties directly affect their interaction with immune systems as well as their in vivo fate and therapeutic effect.Hence,systematic analysis of the physicochemical properties and their effect on in vivo fate is urgently needed.In this review,we frst recapitulate the fundamentals for the in vivo fate of NBCIs including physio-anatomical features of lymphatic system and strategies to modulate immune responses.Moreover,we highlight the effect of physicochemical properties on their in vivo fate including lymph nodes(LNs)drainage,cellular uptake and intracellular transfer.Challenges and opportunities for rational design of NPs for cancer immunotherapy are also discussed in detail.