Probiotic Carriers for Tumor-Targeted Therapy: Applications and Challenges.

Cancer poses an escalating threat to global public health, characterized by continuous rises in both incidence and mortality. While conventional tumor interventions including surgery, chemotherapy and radiotherapy have made considerable progress, their clinical efficacy is severely constrained by systemic toxic side effects, inadequate targeting precision and frequent severe postoperative and treatment-related sequelae. Nanodrug delivery systems have evolved as a viable therapeutic alternative to optimize tumor targeting and minimize systemic toxicity. However, conventional nanocarriers suffer from rapid clearance by the mononuclear phagocyte system, and the intricate, heterogeneous tumor microenvironment (TME) further impairs effective intratumoral drug penetration and uniform distribution. As an emerging class of living delivery vectors, probiotics have recently gained extensive research attention by virtue of their intrinsic tumor tropism, unique capacity to adapt to and remodel the TME, and excellent synergistic compatibility with multiple therapeutic regimens. This review systematically elaborates the biological mechanisms governing the tumor-targeted accumulation and TME-responsive properties of probiotics, summarizes core strategies for probiotic genetic modification and hybrid system construction, and compares the strengths and applicable scenarios of diverse probiotic chassis strains. We further discuss the synergistic potential of probiotic-based platforms combined with immunotherapy, chemotherapy, radiotherapy and physical therapy. Finally, this article underscores the key bottlenecks and future research directions for the clinical translation of probiotic-based antitumor therapeutics, aiming to provide rigorous theoretical support for their broader clinical application in cancer treatment.