Detachable polyzwitterion coated ternary nanoparticles based on peptide dendritic carbon dots for efficient drug delivery in cancer therapy.

In this work, we presented the ternary nanoparticles [pCBMA(CD-D/DOX)] based on peptide dendritic carbon dots (CDs) to realize tumor-specific drug delivery and high efficient cancer therapy. The versatile nanoparticles could achieve "stealth" delivery in blood due to the anti-fouling zwitterion coating. Meanwhile, charge changes of the zwitterions could be moderated during their transportation toward/inside tumor cells, where subtle environmental pH variations acted as potent stimuli to actualize desired functions. In particular, the detachment of the zwitterionic "coat" at tumor site resulted in exposure of the abundant peripheral guanidine groups on peptide dendritic carbon dots (CD-D/DOX) owing to the extracellular pH environment (pH 6.8) induced charge conversion. Consequently, the positively charged CD-D/DOX (+7.02 mV) interacted with the negatively charged cancer cell membrane to enhance cellular uptake. After endocytosis, tumor intracellular microenvironments (acidic condition and high glutathione level) could launch effective disintegration of the CD-D/DOX entities due to acid-induced protonation of guanidine groups and glutathione-induced cleavage of peptide dendritic components on CDs, and then effective endosomal escape and fast doxorubicin hydrochloride (DOX·HCl) release (73.2 % accumulative release within 4 h) were achieved successively. This strategy enabled a 9.19-fold drug release rate at tumor sites in comparison with the one at the physiological environment. Moreover, the excellent fluorescent property of CDs endowed the pCBMA(CD-D/DOX) fluorescence bioimaging function. In view of the above-mentioned advantages, pCBMA(CD-D/DOX) exhibited outstanding anti-tumor activities both in vitro and in vivo, demonstrating much higher anti-tumor efficacy and less side effects than the free DOX·HCl.