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.