Self-Contained Nanocapsules Carrying Anticancer Peptides for Magnetically Activated and Enzyme-Cleaved Drug Delivery

A self-contained nanocapsule for nonspecific cytotoxic anticancer drug delivery and release activated by an enzyme and an alternating magnetic field (AMF) is introduced. This specific prodrug-like drug delivery platform is based on an esterase, an oligomer-based separating barrier, and an ester-linked anticancer peptide melittin encapsulated together in the enlarged pore spaces of the mesoporous silica nanoparticles. A superparamagnetic iron oxide nanoparticle core embedded in the center acts as a nanoheater to stimulate a cascade drug release. Each pore space was designed as a reaction nanovial for the activation of the drug release when the solution inside the nanovial is heated. By employing a thermoresponsive separating barrier as a shield of the peptide drug as well as a separator between the ester-containing peptides and the esterase, the nonspecific cytotoxic effect of the drug and off-target drug release are avoided because the drugs remain inactive in the absence of AMF stimulation. When AMF heating actuates the removal of the separating barrier and exposes the peptide drugs to the enzymes, drug release can be activated. In vivo antitumor experiments further revealed that the nanocapsules exhibited excellent biocompatibility and high tumor-targeting/inhibiting efficiency. The selected esterase, which is in close proximity to the ester-containing peptide drug, efficiently cleaves the ester bonds, thereby causing a catalytic release of peptide drugs and intensified anticancer efficacy.