Significance: The clinical outcomes of anticancer drugs are compromised by their poor physicochemical properties, low tumor targeting, insufficient bioavailability, and side effects. Matrix metalloproteinase 2 (MMP2) has been found overexpressed in most cancers and responsible for tumor cell proliferation and metastasis. In this study, a self-assembling MMP2-sensitive paclitaxel-containing micellar nanopreparation was developed. Several major drug delivery strategies, including self-assembly, PEGylation, the enhanced permeability and retention effect, stimulus sensitivity, a cell-penetrating moiety, and the concept of prodrug, were used in a collaborative fashion to design this nanoparticle. The nanopreparation showed superior tumor targeting, cell internalization, and antitumor efficacy over its nonsensitive counterpart, free paclitaxel and conventional micelles. This uniquely engineered nanoparticle has potential for effective intracellular delivery of drug into cancer cells.

Stimulus-responsive delivery strategies for tumor targeting.