Morphology tunable and acid-sensitive dextran-doxorubicin conjugate assemblies for targeted cancer therapy

Stimuli-responsive and targetable nanomedicine systems have been widely applied as effective modalities for drug delivery and tumor therapeutics. Particle shape is also important for the biodistribution and cellular uptake in drug delivery applications. Here, morphology tunable and acid-responsive dextran-doxorubicin conjugate assemblies of DD-M and DDF-V for targeted doxorubicin (DOX) delivery were constructed, which contains following favorable advantages: (1) One-pot synthesis of drug loaded system with Schiff base reaction was a green chemistry method which is better than conventional drug conjugation/encapsulation ways. (2) The morphology of the nanoparticles could be regulated from micelle (DD-M) to vesicle (DDF-V) by introduction folic acid (FA) or not. (3) The abundant hydroxyl groups and electronegativity make DD-M and DDF-V superior stability in physiological environment. (4) Besides, the multifunctional DDF-V with the important merits including tumor-targeting ability and acid-responsiveness are specific for DOX delivery in cancer therapy. (5) Compared to free DOX and DD-M, DDF-V displayed enhanced anti-tumor efficacy both in vitro and in vivo without obvious systematic toxicity. The morphology tunable, acid-sensitive and targetable nanosystem could be a promising strategy for site-specific drug delivery and potential cancer therapy in the future.