Advancing probiotic delivery in cancer therapy: nanocarrier innovations for enhanced viability, targeted action, and clinical translation
摘要
The escalating global burden of cancer has driven research into leveraging the gut microbiome for innovative therapies, with probiotics emerging as key adjuncts that enhance immune responses, reduce inflammation, and inhibit tumor growth via mechanisms like short-chain fatty acid (SCFA) production and carcinogen detoxification. However, their efficacy is limited by gastrointestinal (GI) degradation, often resulting in > 90% viability loss. This review synthesizes recent advances in nanocarrier-based delivery systems to address these challenges, emphasizing novel strategies that achieve > 90% survival rates in simulated gut conditions and enable precise targeting to the colon or tumor sites. Key innovations include pH-responsive liposomes, polymeric nanoparticles, nanoemulsions, biomimetic exosomes, microfluidic encapsulation, and three-dimensional (3D)-bioprinted matrices, which facilitate synbiotic co-delivery, controlled release, and personalized formulations to amplify anti-cancer effects such as apoptosis induction and immunotherapy synergy. Strain-specific optimizations—e.g., chitosan nanoparticles for Lactobacillus rhamnosus (92–97% encapsulation) or liposomes for Bifidobacterium longum—highlight compatibility-driven enhancements based on cell wall properties and metabolic needs, drawn from 2023 to 2025 studies. Major findings from recent clinical trials (2023–2025) demonstrate translational promise: chitosan-coated Poly(Lactic-co-Glycolic Acid) nanoparticles yielded 63% remission in ulcerative colitis (NCT05878821), liposomal probiotics reduced mucositis by 65% in breast cancer, and folate-targeted PEGylated Poly(Lactic-co-Glycolic Acid) (PEG-PLGA) systems boosted pathological responses by 42% in colorectal cancer. Despite these breakthroughs, challenges in good manufacturing practice (GMP) scaling, biocompatibility, regulatory classification (e.g., Food and Drug Administration (FDA) / European Medicines Agency (EMA) ambiguities), and cost (average development: US$296 million) impede commercialization. By focusing on 2017–2025 preclinical and clinical evidence, this review underscores nanocarriers’ novelty in transforming probiotics into precision tools for microbiome-informed cancer therapy, advocating for larger trials to accelerate clinical adoption.