Inflammatory bowel disease (IBD) is a chronic intestinal inflammatory disorder with a complex pathogenesis involving oxidative stress, intestinal barrier damage, gut microbiota dysbiosis, and immune imbalance. Conventional therapies merely alleviate symptoms but fail to achieve a radical cure, and long-term use is associated with adverse reaction and drug resistance. Probiotics represent a potential therapeutic strategy for IBD by regulating gut microecology, repairing the intestinal barrier, and modulating mucosal immunity, yet their clinical efficacy is severely limited by poor gastrointestinal tolerance, low viability, and inadequate colonization after oral administration. Inspired by bacterial self-protection mechanism, this review highlights innovative biomedical material-based probiotics delivery strategies for IBD, including microencapsulation, single-cell encapsulation, disease-targeted modification, and nanozyme integration. These engineered delivery systems innovatively endow probiotics with acid/bile salt resistance, site-specific targeting to inflamed intestinal mucosa, and reactive oxygen species scavenging capacity, while synergistically optimizing the pathological microenvironment of IBD to enhance probiotics colonization and functional activity. We further emphasize the clinical translation potential of these intelligent delivery platform, and discuss the key design principles for improving their biocompatibility, targeting efficiency, and scalability. This review aims to provide theoretical reference and experimental support for the development of intelligent, efficient probiotics delivery system with clinical translation potential, which may help address the unmet therapeutic needs of IBD and act as a novel adjunctive therapy for clinical practice in the future.

Inflammatory bowel disease (IBD) is featured by chronic intestinal inflammation, oxidative stress imbalance, impaired intestinal barrier and gut microbiota dysbiosis. Clinically, safe and efficient therapeutic regimens capable of realizing precise targeting, robust antioxidation and gut microbiota homeostasis restoration are still in urgent demand. Excessive intestinal accumulation of reactive oxygen species (ROS) acts as a core inducer of inflammatory exacerbation, mucosal injury and tissue fibrosis. Nevertheless, conventional small-molecule antioxidants are restricted by poor targeting capability and unsatisfactory in vivo stability, which greatly hampers their long-term ROS-scavenging performance. Recently, functional nanomaterials with multi-enzyme-mimicking properties have been developed to mimic endogenous antioxidant systems, facilitating in situ clearance of redundant ROS, suppression of proinflammatory cascades and maintenance of intestinal epithelial integrity. Combined with overexpressed receptors in the inflammatory microenvironment of IBD, can substantially enhance the oral stability, lesion accumulation and synergistic therapeutic efficiency of these biomaterials. This review systematically summarizes recent research advances in enzyme-mimetic targeted biomaterials, intelligent drug delivery carriers and engineered probiotics platforms against IBD. We particularly elaborate the developmental trend shifting from independent antioxidant treatment and targeted drug delivery toward synergistic therapy based on nanozyme and probiotics. Importantly, unstable nanozyme catalytic activity, unsatisfactory in vivo adaptability, uncontrollable probiotics colonization and bottlenecks of engineered probiotics for clinical transformation are comprehensively discussed. Eventually, future prospects of next-generation oral formulations with biodegradability, stimulus responsiveness and multi-target synergistic effects are proposed, providing theoretical references and innovative clues for developing safe, effective and precisely targeted therapeutic candidates for IBD.

Tumor heterogeneity, immune-suppressive microenvironment and the precise killing of tumor cells by drugs are important factors affecting tumor treatment. In this study, we developed environment-responsive drug delivery system (FM@IQ/PST&ZIF-8/DOX) based on ZIF-8 for tumor photothermal/immunotherapy/chemotherapy synergistic therapy. The prepared FM@IQ/PST&ZIF-8/DOX nanoplatfrom not only has highly drug loading capacity for chemotherapeutic drug-doxorubicin, but also erythrocyte membrance modified on their surface can endow their immunity-escaping property and prolong their blood circulation time. More important, the neurotransmitter serotonin was encapsulated on the surface of ZIF-8/DOX by oxidative polymerization, which can effectively avoid the premature leakage of DOX in the blood circulation. And the formed polyserotonin shell has superior photothermal conversion performance, as well as the adsorption property of polyserotonin shell was utilized to load imiqumod. When FM@IQ/PST&ZIF-8/DOX entered the tumor tissue, the surface modified folate molecules can specifically bind to the folate receptors on the surface of tumor cells to improve FM@IQ/PST&ZIF-8/DOX uptake by tumor cells. In vitro and in vivo results showed that FM@IQ/PST&ZIF-8/DOX nanoplatform could generate a large amount of heat under near-infrared light irradiation, and then induce the apoptosis of tumor cells, release tumor associated antigens, and effectively solve the problem of tumor heterogeneity. In addition, the loaded imiquimod could effectively improve the immunosuppressive microenvironment, enhance the body’s anti-tumor immune response, to inhibit tumor metastasis and recurrence. Therefore, the novel FM@IQ/PST&ZIF-8/DOX nanoplatform designed in this research can not only achieve controllable and precise drug release, but also it is expected to become a promising new strategy for tumor treatment and provide corresponding inspiration for the later research and development of environment-responsive drugs.

Tumor vaccine, which can effectively prevent tumor recurrence and metastasis, is a promising tool in tumor immunotherapy. However, heterogeneity of tumors and the inability to achieve a cascade effect limit the therapeutic effects of most developing tumor vaccine. We have developed a cascading immunoinducible in-situ mannose-functionalized polydopamine loaded with imiquimod phenylboronic hyaluronic acid nanocomposite gel vaccine (M/P-PDA@IQ PHA) through a boronic ester-based reaction. This reaction utilizes mannose-functionalized polydopamine loaded with imiquimod (M/P-PDA@IQ NAs) as a cross-linking agent to react with phenylboronic-grafted hyaluronic acid. Under near-infrared light irradiation, the M/P-PDA@IQ PHA caused local hyperthermia to trigger immunogenic cell death of tumor cells and tumor-associated antigens (TAAs) releasing. Subsequently, the M/P-PDA@IQ NAs which were gradually released by the pH/ROS/GSH-triggered degradation of M/P-PDA@IQ PHA, could capture and deliver these TAAs to lymph nodes. Finally, the M/P-PDA@IQ NAs facilitated maturation and cross-presentation of dendritic cells, as well as activation of cytotoxic T lymphocytes. Overall, the M/P-PDA@IQ PHA could serve as a novel in situ vaccine to stimulate several key nodes including TAAs release and capture, targeting lymph nodes and enhanced dendritic cells uptake and maturation as well as T cells activation. This cascading immune activation strategy can effectively elicit antitumor immune response.

Myocardial infarction-associated transcript (MIAT) is a long noncoding RNA that plays a critical role in a variety of diseases. Accordingly, this study probed into the possible interaction mechanism between MIAT and miR-378a-5p in breast cancer. Concretely, MIAT and miR-378a-5p expressions in breast cancer tissues and cells were measured. After transfection with siMIAT and miR-378a-5p inhibitor, the viability and proliferation of breast cancer cells were examined by cell counting kit-8 and colony formation assays. The expressions of apoptosis-related proteins were detected. According to the results, MIAT was highly expressed in breast cancer tissues and cells. MIAT silencing could decrease Bcl-2 expression, viability, and proliferation of breast cancer cells and increase the expressions of cleaved caspase-3 and Bax. MIAT and miR-378a-5p could directly bind to each other, and MIAT silencing promoted the expression of miR-378a-5p. miR-378a-5p expression was low in breast cancer tissues. The miR-378a-5p inhibitor enhanced the viability and proliferation of breast cancer cells and partially reversed the effects of MIAT silencing on the breast cancer cells. In conclusion, MIAT silencing inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p, indicating the potential of MIAT as a new target for the treatment of breast cancer.

Phototherapy has been recognized as a photochemical process to treat tumor via induce cancer cells necrosis and death, with minimal invasiveness, higher selectivity, and few side effects. However, the therapy effects of phototherapy are often compromised by the hypoxia, high levels of hydrogen peroxide, and glutathione of tumor microenvironment (TME). Therefore, we constructed a catalase-like activity bionic metal–organic framework drugs delivery system (FA-EM@MnO2/ZIF-8/ICG) with tumor microenvironment controllable releasing. In this system, photosensitizer indocyanine green (ICG) was introduced into zeolite imidazole salt skeleton 8 (ZIF-8) by one-step methods, forming ZIF-8/ICG nano-platform, which can effectively avoid ICG-induced phototoxicity and aggregation-induced quenching during transport. MnO2 with catalase-like activity was coated on the surface of ZIF-8/ICG nano-platform, which made it have the ability of self-supplying O2 under the condition of H2O2 in TME. Exposure under near-infrared light can alleviate the anoxic TME, thus improving the phototherapy efficiency. In addition, folate-functionalized erythrocyte membrane is coated on the surface of MnO2/ZIF-8/ICG, which can endow FA-EM@MnO2/ZIF-8/ICG with the ability of targeted drug administration and immune elimination avoidance. Therefore, FA-EM@MnO2/ZIF-8/ICG nano-platform has the catalase-like activity, which can alleviate the oxidative stress state of TME and provide a beneficial environment for photodynamic therapy of tumor.

Nanoparticles have unique properties and high design flexibility, which are thought to be safe, site-specific, and efficient drug delivery systems. However, nanoparticles as exogenous materials can provide recognition and be eliminated by the body’s immune system, which considerably restricts their applications. To overcome these drawbacks, natural cell membrane coating method has attracted great attention in the field of drug delivery systems, which can prolong nanoparticles blood circulation time and avoiding the capture as well as elimination by the body immune system. Biomimetic nanoparticles via a top-down approach can avoid the laborious group modified engineering and keep the integrity of cell membrane structure and membrane antigens, which can be endowed with unique properties, such as immune escape, longer blood circulation time, targeting delivery and controlling drugs sustain-release. At the present research, erythrocyte membrane, cancer cell membrane, platelet membrane, lymphocyte membrane and hybrid membrane have been successfully coated into the surface of nanoparticles to achieve biological camouflage. Thus, integrating various kinds of cell membranes and nanoparticles into one system, the biomimetic nanoparticles can inherit unique biofunction and drug delivery properties to exhibit tumor targeting-delivery and antitumor outcomes. In this article, we will discuss the prospects and challenges of some basic cell membrane cloaking nanoparticles as a drug delivery system for cancer therapy.

Nanoparticles as drug delivery systems can alter the drugs' hydrophilicity to affect drug uptake and efflux in tissues. They prevent drugs from non-specifically binding with bio-macromolecules and enhance drug accumulation at the lesion sites, improving therapy effects and reducing unnecessary side effects. Metal–organic frameworks (MOFs), the typical nanoparticles, a class of crystalline porous materials via self-assembled organic linkers and metal ions, exhibit excellent biodegradability, pore shape and sizes, and finely tunable chemical composition. MOFs have a rigid molecular structure, and tunable pore size can improve the encapsulation drug's stability under harsh conditions. Besides, the surface of MOFs can be modified with small-molecule ligands and biomolecule, and binding with the biomarkers which is overexpressed on the surface of cancer cells. MOFs formulations for therapeutic have been developed to effectively respond to the unique tumor microenvironment (TEM), such as high H2O2 levels, hypoxia, and high concentration glutathione (GSH). Thus, MOFs as a drug delivery system should avoid drugs leaking during blood circulation and releasing at the lesion sites via a controlling manner. In this article, we will summary environment responsive MOFs as drug delivery systems for tumor therapy under different stimuli.