Anti-biofouling therapeutic nanoparticles with removable shell and highly efficient internalization by cancer cells

Cationic gelatin nanoparticles ((+)nGNPs) were prepared by in situ polymerization upon the surfaces of monodispersed gelatin nanoparticles (GNPs) using N-(3-Aminopropyl)methacrylamide (APm) as monomer, which were then decorated with doxorubicin terminated poly(2-methylacryloyloxyethyl phosphorylcholine) (DOX-pMPC) via EDC/NHS conjugation to obtain core–shell nanoparticles ((+)nGNPs@DOX-pMPC) for cancer therapy. The non-fouling pMPC shell could effectively shield the positively charged surface of inner nanoparticle and prevent non-specific protein adsorption, thus endowing the materials with potential for long-acting cancer treatment. Furthermore, the acyl hydrazone bond connecting DOX and pMPC chain could be easily hydrolyzed in the weakly acidic tumor microenvironment. After decladding of the pMPC shell, electropositive (+)nGNPs carrying the drugs can be effectively internalized by cancer cells to induce apoptosis, avoiding undesirable hindrance caused by the superhydrophilic outer layer. On combining the above properties, this drug delivery system can be a promising candidate for long-acting, low-toxicity and high-efficiency cancer therapy.