A porphyrin metal–organic framework enhances photodynamic therapy through lymphatic circulation

Photodynamic therapy (PDT) has emerged as a promising strategy for cancer treatment as a local and precise therapeutic technique. However, lymph node metastasis of tumors poses a therapeutic challenge. To increase PDT's <i>in vivo</i> cancer effectiveness, direct targeting of lymph nodes (LNs) is the most promising approach. Herein, based on the targeting of hyaluronic acid (HA) to lymphatic endothelial cells, surface modification of porphyrin metal-organic frameworks (MOFs) was conducted to improve the therapeutic efficacy of PDT on lymphatic metastatic tumors. In this system, the prepared HA-MOFs produced equivalent reactive oxygen species (ROS) under the same light exposure as in the case of MOFs, producing consistent <i>in vitro</i> toxicity to tumor cells. After subcutaneous injection in mice, HA-MOFs preferentially accumulated in nearby inguinal LNs and circulated to the tumor site <i>via</i> the lymphatic system. <i>In vivo</i> experiments demonstrated that HA-MOFs circulated to the tumor site through the lymph, generating a more effective PDT therapeutic effect and significantly prolonging the median survival of hormonal mice. In conclusion, studies have demonstrated that HA-MOFs act as a powerful therapeutic platform to deliver drugs to LNs through lymphatic circulation to enhance tumor therapy.