Engineering Phototheranostic Nanoscale Metal–Organic Frameworks for Multimodal Imaging-Guided Cancer Therapy

TLDR

Many photoresponsive dyes have been used for imaging and photodynamic/photothermal therapy, but the only FDA‑approved near‑infrared dye, indocyanine green, suffers from poor solubility, low cancer specificity, and limited sensitivity. To address these limitations, the authors engineered a multifunctional nanoplatform comprising hyaluronic acid–coated MIL‑100(Fe) metal‑organic framework nanoparticles loaded with indocyanine green for imaging‑guided anticancer photothermal therapy. The HA‑MOF@ICG nanoparticles achieved a 40 % ICG loading, strong NIR absorbance, photostability, and CD44‑mediated tumor targeting, resulting in enhanced cellular uptake and tumor accumulation compared with non‑targeted MOF@ICG and free ICG. In vitro and in vivo studies demonstrated that the HA‑MOF@ICG nanoparticles effectively inhibited MCF‑7 cell growth and xenograft tumor progression, establishing them as a promising theranostic platform for cancer‑specific, image‑guided photothermal therapy.

Abstract

Many photoresponsive dyes have been utilized as imaging and photodynamic/photothermal therapy agents. Indocyanine green (ICG) is the only near-infrared region (NIR) organic dye for clinical applications approved by the United States Food and Drug Administration; however, the clinical application of ICG is limited by its poor aqueous solubility, low cancer specificity, and low sensitivity in cancer theranostics. To overcome these issues, a multifunctional nanoplatform based on hyaluronic acid (HA) and ICG-engineered metal-organic framework MIL-100(Fe) nanoparticles (MOF@HA@ICG NPs) was successfully developed for imaging-guided, anticancer photothermal therapy (PTT). The synthesized NPs showed a high loading content of ICG (40%), strong NIR absorbance, and photostability. The in vitro and in vivo imaging showed that the MOF@HA@ICG NPs exhibited greater cellular uptake in CD44-positive MCF-7 cells and enhanced tumor accumulation in xenograft tumors due to their targeting capability, compared to MOF@ICG NPs (non-HA-targeted) and free ICG. The in vitro photothermal toxicity and in vivo PTT treatments demonstrated that MOF@HA@ICG NPs could effectively inhibit the growth of MCF-7 cells/xenograft tumors. These results suggest that MOF@HA@ICG NPs could be served as a new promising theranostic nanoplatform for improved anticancer PTT through cancer-specific and image-guided drug delivery.