MOF × Biopolymer: Collaborative Combination of Metal–Organic Framework and Biopolymer for Advanced Anticancer Therapy

Metal-organic framework (MOF) nanoparticles with high porosity and greater tunability have emerged as new drug delivery vehicles. However, premature drug release still remains a challenge in the MOF delivery system. Here, we report an enzyme-responsive, polymer-coated MOF gatekeeper system using hyaluronic acid (HA) and PCN-224 nanoMOF. The external surface of nanoMOF can be stably covered by HA through multivalent coordination bonding between the Zr cluster and carboxylic acid of HA, which acts as a gatekeeper. HA allows selective accumulation of drug carriers in CD44 overexpressed cancer cells and enzyme-responsive drug release in the cancer cell environment. In particular, inherent characteristics of PCN-224, which is used as a drug carrier, facilitates the transfer of the drug to cancer cells more stably and allows photodynamic therapy. This HA-PCN system enables a dual chemo and photodynamic therapy to enhance the cancer therapy effect.