Gut microbiota have close interactions with the host. It can affect cancer progression and the outcomes of cancer therapy, including chemotherapy, immunotherapy, and radiotherapy. Therefore, approaches toward the modulation of gut microbiota will enhance cancer prevention and treatment. Modern drug delivery systems (DDS) are emerging as rational and promising tools for microbiota intervention. These delivery systems have compensated for the obstacles associated with traditional treatments. In this review, the essential roles of gut microbiota in carcinogenesis, cancer progression, and various cancer therapies are first introduced. Next, advances in DDS that are aimed at enhancing the efficacy of cancer therapy by modulating or engineering gut microbiota are highlighted. Finally, the challenges and opportunities associated with the application of DDS targeting gut microbiota for cancer prevention and treatment are briefly discussed.

The red blood cell membrane (RBCm) provides tight protection, lowers the immunogenicity, and prolongs the circulation time of drugs in vivo when acting as the coating of drug delivery systems. However, the cellular uptake and release of drugs are hindered by RBCm. Docetaxel (DTX) is the first-line medicine for treating triple-negative breast cancer (TNBC), but it induces tumor metastasis. To solve these dilemmas, in this study, the photosensitizer 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DiR)-modified RBCm (DM) is prepared, which is coated onto a hybrid micelle consisting of the prodrugs of DTX and the anti-metastasis agent calcitriol (CTL), obtaining a nanoparticle, named HDC-DM. In a 4T1 tumor-bearing mouse model, after injecting HDC-DM, the intratumoral DTX and CTL concentrations are increased by 1.7 and 2.5 times compared with the free drug groups. After irradiating tumors with near-infrared laser, DiR elicits the photothermal effect, triggering the rupture of RBCm and drug release, promoting drug penetration in tumors, and inducing immunogenic cell death. The tumor growth inhibition rate is 77%, and the formation of lung metastases is reduced by 82%, with good biocompatibility. It is suggested that the combination of phototherapy, chemotherapy, and anti-metastatic therapy using HDC-DM is expected to be a powerful strategy for treating TNBC.