Recent advances in zwitterionic nanoscale drug delivery systems to overcome biological barriers

Nanoscale drug delivery systems(nDDS)have been employed widely in enhancing the therapeutic efficacy of drugs against diseases with reduced side effects.Although several nDDS have been successfully approved for clinical use up to now,biological barriers between the administration site and the target site hinder the wider clinical adoption of nDDS in disease treatment.Polyethylene glycol(PEG)-modification(or PEGylation)has been regarded as the gold standard for stabilising nDDS in complex biological environment.However,the accelerated blood clearance(ABC)of PEGylated nDDS after repeated injections becomes great challenges for their clinical applications.Zwitterionic polymer,a novel family of antifouling materials,have evolved as an alternative to PEG due to their super-hydrophilicity and biocompatibility.Zwitterionic nDDS could avoid the generation of ABC phenomenon and exhibit longer blood circulation time than the PEGylated analogues.More impressively,zwitterionic nDDS have recently been shown to overcome multiple biological barriers such as nonspecific organ distribution,pressure gradients,impermeable cell membranes and lysosomal degradation without the need of any complex chemical modifications.The realization of overcoming multiple biological barriers by zwitterionic nDDS may simplify the current overly complex design of nDDS,which could facilitate their better clinical translation.Herein,we summarise the recent progress of zwitterionic nDDS at overcoming various biological barriers and analyse their underlyingmechanisms.Finally,prospects and challenges are introduced to guide the rational design of zwitterionic nDDS for disease treatment.

Rapid sterilisation and diabetic cutaneous regeneration using cascade bio-heterojunctions through glucose oxidase-primed therapy

The cutaneous wound in diabetic patients frequently encounters intractable pathogenic infections due to the hyperglycemia micromilieu which is conducive to bacterial growth and multiplication.Despite the extensive clinical use of antibiotics to treat bacterial infections,the emergence of drug-resistant and super pathogens as well as the potential side effects of antibiotics have elicited alarming challenges to public health.To address this daunting concern,we devise and develop a photo-activated cascade bio-heterojunctions(C-bio-HJs)for rapid sterilization and diabetic cutaneous regeneration.In the designed C-bio-HJs,photo-generated electron-hole pairs of graphite-phase carbon nitride(g-C_(3)N_(4))are effectively separated with the marriage of molybdenum disulfide(MoS_(2)),which achieves the augmented photodynamic antibacterial effect.Moreover,glucose oxidase(GOx)tethered on the bio-HJs catalyzes glucose into hydrogen peroxide(H_(2)O_(2))in diabetic wounds for starvation therapy.Furthermore,Mo4+enables the catalysis of H_(2)O_(2)into a highly effective hydroxyl radical(⋅OH)for chemodynamic-photothermal combined antibacterial therapy.Both in vitro and in vivo results authenticate the cascading antibacterial properties and skin regeneration-promoting effects of the C-bio-HJs,which provide a facile strategy to combat diabetic wound healing through the synergistic GOx-primed dynamic therapies.