Biodegradable Cyclomatrix Polyphosphazene Nanoparticles: A Novel pH-Responsive Drug Self-Framed Delivery System

Traditional drug delivery systems suffer from low drug-loading and relatively weak therapeutic efficacy, therefore, development of new drug delivery systems with high-efficiency has become more urgent. In this report, a novel-innovative drug delivery strategy, namely drug self-framed delivery system (DSFDS), is prepared via using anticancer drugs as polymer frame without using any carriers. The drug molecules (exemplified by doxorubicin) containing more than two nucleophilic functional groups (diols/diamines) directly reacted with hexachlorocyclotriphosphazene via mild precipitation polycondensation under ambient conditions, forming biocompatible drug self-framed delivery nanoparticles. Because of the covalent bonding of the drug molecules, DSFD nanoparticles (DSFDs) with super high drug-loading were stable in the circulation during delivery. However, sustained release of drug in the acidic environment within cells endowed DSFDs with long-term anticancer therapeutic efficacy. This strategy is applicable for diverse hydrophilic and hydrophobic drugs and may be a new platform for designing high drug -loading and release-controllable drug delivery systems.