Metal-Organic Frameworks Nucleated by Silk Fibroin and Modified with Tumor-Targeting Peptides for Targeted Multimodal Cancer Therapy.

Multimodal therapy requires effective drug carriers that can deliver multiple drugs to specific locations in a controlled manner. Here, the study presents a novel nanoplatform constructed using zeolitic imidazolate framework-8 (ZIF-8), a nanoscale metal-organic framework nucleated under the mediation of silk fibroin (SF). The nanoplatform is modified with the newly discovered MCF-7 breast tumor-targeting peptide, AREYGTRFSLIGGYR (AR peptide). Indocyanine green (ICG) and doxorubicin (DOX) are loaded onto the nanoplatform with high drug encapsulation efficiency (>95%). ICG enables the resultant nanoparticles (NPs), called AR-ZS/ID-P, to release reactive oxygen species for photodynamic therapy (PDT) and heat for photothermal therapy (PTT) under near-infrared (NIR) irradiation, promoting NIR fluorescence and thermal imaging to guide DOX-induced chemotherapy. Additionally, the controlled release of both ICG and DOX at acidic tumor conditions due to the dissolution of ZIF-8 provides a drug-targeting mechanism in addition to the AR peptide. When intravenously injected, AR-ZS/ID-P NPs specifically target breast tumors and exhibit higher anticancer efficacy than other groups through ICG-enabled PDT and PTT and DOX-derived chemotherapy, without inducing side effects. The results demonstrate that AR-ZS/ID-P NPs are a promising multimodal theranostic nanoplatform with maximal therapeutic efficacy and minimal side effects for targeted and controllable drug delivery.