Biomimetic nanoparticles in gastrointestinal cancer therapy: Multimodal strategies, targeted delivery, and clinical perspectives

Gastrointestinal (GI) cancers, including gastric, colorectal, liver, esophageal, and pancreatic cancers, represent a significant global health burden due to late diagnosis, drug resistance, and limited therapeutic efficacy. Biomimetic nanoparticles (NPs) have emerged as innovative drug carriers for targeted cancer therapy due to their enhanced biocompatibility and selective accumulation in tumor tissues, which can obviate challenges such as systemic toxicity and drug resistance. In this review, we have summarized the different biomimetic NPs, including cell membrane-coated NPs, metal-organic frameworks, and hybrid nanosystems, which integrate multiple therapeutic modalities such as photothermal therapy, chemotherapy, immunotherapy, and gene editing. Furthermore, the use of biomimetic NPs for dual-modality imaging, pH-sensitive drug release, and synergistic treatment strategies have also been highlighted, along with mechanisms such as mitochondrial targeting, ferroptosis induction, and immune modulation. Finally, we have discussed the current preclinical and clinical evidence on the efficacy and biosafety of these biomimetic NPs in cancer treatment, and emphasized their potential for personalized therapeutic approaches. This graphical abstract illustrates the multifunctional applications of biomimetic nanoparticles in gastrointestinal cancer therapy. It highlights the use of biomimetic nanoparticles in different gastrointestinal sites (stomach, colorectum, liver, esophagus, and pancreas) in combination with various therapeutic modalities such as photothermal therapy, photodynamic therapy, chemodynamic therapy, and chemotherapy, demonstrating their capability to integrate multiple treatment approaches. • Biomimetic nanoparticles reduce systemic toxicity and treatment resistance through targeted drug delivery. • Cell membrane-coated and hybrid Biomimetic nanoparticles enable synergistic photothermal, chemo-, and immunotherapy. • Dual-modality imaging, pH-sensitive drug release, and mitochondria-targeted delivery can further enhance therapeutic precision. • Preclinical and clinical studies show improved tumor suppression, reduced metastasis, and fewer off-target effects. • Immune modulation, ferroptosis induction, and precision delivery highlight their potential in personalized therapy.