Efficiently directing differentiation and homing of mesenchymal stem cells to boost cartilage repair in osteoarthritis via a nanoparticle and peptide dual-engineering strategy.

Mesenchymal stem cells (MSCs) are expected to be useful therapeutics in osteoarthritis (OA), the most common joint disorder characterized by cartilage degradation. However, evidence is limited with regard to cartilage repair in clinical trials because of the uncontrolled differentiation and weak cartilage-targeting ability of MSCs after injection. To overcome these drawbacks, here we synthesized CuO@MSN nanoparticles (NPs) to deliver Sox9 plasmid DNA (favoring chondrogenesis) and recombinant protein Bmp7 (inhibiting hypertrophy). After taking up CuO@MSN/Sox9/Bmp7 (CSB NPs), the expressions of chondrogenic markers were enhanced while hypertrophic markers were decreased in response to these CSB-engineered MSCs. Moreover, a cartilage-targeted peptide (designated as peptide W) was conjugated onto the surface of MSCs via a click chemistry reaction, thereby prolonging the residence time of MSCs in both the knee joint cavity of mice and human-derived cartilage. In a surgery-induced OA mouse model, the NP and peptide dual-modified W-CSB-MSCs showed an enhancing therapeutic effect on cartilage repair in knee joints compared with other engineered MSCs after intra-articular injection. Most importantly, W-CSB-MSCs accelerated cartilage regeneration in damaged cartilage explants derived from OA patients. Thus, this new peptide and NPs dual engineering strategy shows potential for clinical applications to boost cartilage repair in OA using MSC therapy.

Photoswitchable dynamics and RNAi synergist with tailored interface and controlled release reprogramming tumor immunosuppressive niche.

Immunosuppressive tumor microenvironment (ITM) severely limited the efficacy of immunotherapy against triple-negative breast cancer (TNBC). Herein, Apt-LPR, a light-activatable photodynamic therapy (PDT)/RNAi immune synergy-enhancer was constructed by co-loading miR-34a and photosensitizers in cationic liposomes (in phase III clinical trial). Interestingly, the introduction of tumor-specific aptamers creates a special "Liposome-Aptamer-Target" interface, where the aptamers are initially in a "lying down" state but transform to "standing up" after target binding. The interfacing mechanism was elaborately revealed by computational and practical experiments. This unique interface endowed Apt-LPR with neutralized surface potential of cationic liposomes to reduce non-specific cytotoxicity, enhanced DNase resistance to protect aptamers, and preserved target-binding ability for selective drug delivery. Upon near-infrared irradiation, the generated reactive oxygen species would oxidize unsaturated phospholipids to destabilize both liposomes and lysosomes, realizing stepwise lysosomal escape of miR-34a for tumor cell apoptosis and downregulation of PD-L1 to suppress immune escape. Together, tumor-associated antigens released from PDT-damaged mitochondria and endoplasmic reticulum could activate the suppressive immune cells to establish an "immune hot" milieu. The collaborative immune-enhancing strategy effectively aroused systemic antitumor immunity and inhibited primary and distal tumor progression as well as lung metastasis in 4T1 xenografted mouse models. The photo-controlled drug release and specific tumor-targeting capabilities of Apt-LPR were also visualized in MDA-MB-231 xenografted zebrafish models. Therefore, this photoswitchable PDT/RNAi immune stimulator offered a powerful approach to reprogramming ITM and reinforcing cancer immunotherapy efficacy.

Inflammatory stimulus-responsive polymersomes reprogramming glucose metabolism mitigates rheumatoid arthritis.

Inflammation-resident cells within arthritic sites undergo a metabolic shift towards glycolysis, which greatly aggravates rheumatoid arthritis (RA). Reprogramming glucose metabolism can suppress abnormal proliferation and activation of inflammation-related cells without affecting normal cells, holding potential for RA therapy. Single 2-deoxy-d-glucose (2-DG, glycolysis inhibitor) treatment often cause elevated ROS, which is detrimental to RA remission. The rational combination of glycolysis inhibition with anti-inflammatory intervention might cooperatively achieve favorable RA therapy. To improve drug bioavailability and exert synergetic effect, stable co-encapsulation of drugs in long circulation and timely drug release in inflamed milieu is highly desirable. Herein, we designed a stimulus-responsive hyaluronic acid-triglycerol monostearate polymersomes (HTDD) co-delivering 2-DG and dexamethasone (Dex) to arthritic sites. After intravenous injection, HTDD polymersomes facilitated prolonged circulation and preferential distribution in inflamed sites, where overexpressed matrix metalloproteinases and acidic pH triggered drug release. Results indicated 2-DG can inhibit the excessive cell proliferation and activation, and improve Dex bioavailability by reducing Dex efflux. Dex can suppress inflammatory signaling and prevent 2-DG-induced oxidative stress. Thus, the combinational strategy ultimately mitigated RA by inhibiting glycolysis and hindering inflammatory signaling. Our study demonstrated the great potential in RA therapy by reprogramming glucose metabolism in arthritic sites.

Macrophage targeted graphene oxide nanosystem synergize antibiotic killing and host immune defense for Tuberculosis Therapy.

Tuberculosis (TB), a deadly disease caused by Mycobacterium tuberculosis (Mtb) infection, remains one of the top killers among infectious diseases worldwide. How to increase targeting effects of current anti-TB chemotherapeutics and enhance anti-TB immunological responses remains a big challenge in TB and drug-resistant TB treatment. Here, mannose functionalized and polyetherimide protected graphene oxide system (GO-PEI-MAN) was designed for macrophage-targeted antibiotic (rifampicin) and autophagy inducer (carbamazepine) delivery to achieve more effective Mtb killings by combining targeted drug killing and host immunological clearance. GO-PEI-MAN system demonstrated selective uptake by in vitro macrophages and ex vivo macrophages from macaques. The endocytosed GO-PEI-MAN system would be transported into lysosomes, where the drug loaded Rif@Car@GO-PEI-MAN system would undergo accelerated drug release in acidic lysosomal conditions. Rif@Car@GO-PEI-MAN could significantly promote autophagy and apoptosis in Mtb infected macrophages, as well as induce anti-bacterial M1 polarization of Mtb infected macrophages to increase anti-bacterial IFN-γ and nitric oxide production. Collectively, Rif@Car@GO-PEI-MAN demonstrated effectively enhanced intracellular Mtb killing effects than rifampicin, carbamazepine or GO-PEI-MAN alone in Mtb infected macrophages, and could significantly reduce mycobacterial burdens in the lung of infected mice with alleviated pathology and inflammation without systemic toxicity. This macrophage targeted nanosystem synergizing increased drug killing efficiency and enhanced host immunological defense may be served as more effective therapeutics against TB and drug-resistant TB.

Influencing factors and solution strategies of chimeric antigen receptor T-cell therapy (CAR-T) cell immunotherapy.

Chimeric antigen receptor T-cesll therapy (CAR-T) has achieved groundbreaking advancements in clinical application, ushering in a new era for innovative cancer treatment. However, the challenges associated with implementing this novel targeted cell therapy are increasingly significant. Particularly in the clinical management of solid tumors, obstacles such as the immunosuppressive effects of the tumor microenvironment, limited local tumor infiltration capability of CAR-T cells, heterogeneity of tumor targeting antigens, uncertainties surrounding CAR-T quality, control, and clinical adverse reactions have contributed to increased drug resistance and decreased compliance in tumor therapy. These factors have significantly impeded the widespread adoption and utilization of this therapeutic approach. In this paper, we comprehensively analyze recent preclinical and clinical reports on CAR-T therapy while summarizing crucial factors influencing its efficacy. Furthermore, we aim to identify existing solution strategies and explore their current research status. Through this review article, our objective is to broaden perspectives for further exploration into CAR-T therapy strategies and their clinical applications.

Evaluation of the effect of RNA secondary structure on Cas13d-mediated target RNA cleavage.

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas13d system was adapted as a powerful tool for targeting viral RNA sequences, making it a promising approach for antiviral strategies. Understanding the influence of template RNA structure on Cas13d binding and cleavage efficiency is crucial for optimizing its therapeutic potential. In this study, we investigated the effect of local RNA secondary structure on Cas13d activity. To do so, we varied the stability of a hairpin structure containing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) target sequence, allowing us to determine the threshold RNA stability at which Cas13d activity is affected. Our results demonstrate that Cas13d possesses the ability to effectively bind and cleave highly stable RNA structures. Notably, we only observed a decrease in Cas13d activity in the case of exceptionally stable RNA hairpins with completely base-paired stems, which are rarely encountered in natural RNA molecules. A comparison of Cas13d and RNA interference (RNAi)-mediated cleavage of the same RNA targets demonstrated that RNAi is more sensitive for local target RNA structures than Cas13d. These results underscore the suitability of the CRISPR-Cas13d system for targeting viruses with highly structured RNA genomes.

Advancements in precision nanomedicine design targeting the anoikis-platelet interface of circulating tumor cells.

Tumor metastasis, the apex of cancer progression, poses a formidable challenge in therapeutic endeavors. Circulating tumor cells (CTCs), resilient entities originating from primary tumors or their metastases, significantly contribute to this process by demonstrating remarkable adaptability. They survive shear stress, resist anoikis, evade immune surveillance, and thwart chemotherapy. This comprehensive review aims to elucidate the intricate landscape of CTC formation, metastatic mechanisms, and the myriad factors influencing their behavior. Integral signaling pathways, such as integrin-related signaling, cellular autophagy, epithelial-mesenchymal transition, and interactions with platelets, are examined in detail. Furthermore, we explore the realm of precision nanomedicine design, with a specific emphasis on the anoikis‒platelet interface. This innovative approach strategically targets CTC survival mechanisms, offering promising avenues for combatting metastatic cancer with unprecedented precision and efficacy. The review underscores the indispensable role of the rational design of platelet-based nanomedicine in the pursuit of restraining CTC-driven metastasis.

Phantom-Enhanced High Mechanical Accuracy for Frame-Based Deep Brain Stimulation.

Deep brain stimulation (DBS) is a neurosurgical procedure that depends on high-accuracy targeting of structures to implant electrodes within the brain. The positioning of these electrodes in the brain determines the long-term efficacy of treating diseases such as Parkinson's disease, essential tremor, or dystonia. Misplaced electrodes in DBS can lead to poor efficacy and stimulation-induced side effects. Widespread targeting errors and variability have been published throughout the literature. As such, improvement in targeting accuracy is needed to enhance the quality of the procedures. A stereotactic phantom was utilized to test and adjust targeting before the surgical placement in the brain for 91 sequential electrodes. The tip of the microelectrode, the first rigid point in time, was measured and compared to the planned target. The technique utilized a to-target cannula with an XY stage that allowed x-axis and y-axis adjustments and correction for inaccuracies relative to the phantom. A calculation was developed to convert anatomical angles (sagittal and coronal) provided by commercial planning stations to spherical angles to calculate points along a trajectory. Error calculations included each dimensional axis, Euclidean error, and radial error. Bends in the cannula and microelectrode were observed and corrected by referencing the phantom. All 91 first-pass tracks traversed the intended target, and three electrodes required a second mapping track beyond the first penetration due to neurophysiological and intraoperative testing. The results showed overall ultra-high (0-0.5 mm) to high (>0.5-1 mm) accuracy, an average Euclidean error of 0.66±0.30 mm, and a radial error of 0.45±0.28 mm with dimensional errors of less than 0.5 mm per axis. The utilization of a stereotactic phantom is an important tool to enhance the stereotactic targeting before insertion into the brain. This phantom technique yielded ultra-high to high accuracy in error calculations. Future methods and studies should focus on error minimization to enhance these DBS mechanical accuracy and correlations with clinical outcomes.

Lipopolysaccharide targeting-peptide-capped chitosan gold nanoparticles for laser-induced antibacterial activity.

Aim: We present the synthesis of anti-bacterial gold nanoparticles using chitosan as a dual-functional agent. The resulting ChAuNPs were further modified with a lipopolysaccharide-targeting antibacterial peptide to aid in biocompatibility and specificity.Materials & methods: The nanoparticles' antibacterial activity against Escherichia coli was tested in the presence of a 450 nm laser.Results: Our data suggested that the peptide and laser emissions had a synergistic impact on the gold nanoparticles, resulting in strong antibacterial effects. The study shows that advanced nanomaterials, including chitosan, gold nanoparticles and lipopolysaccharide targeting peptides, can boost antibacterial functions at a low concentration of 250 µg/ml.Conclusion: The findings highlight ChAuNPs' potential as strong antibacterial agents, with targeted alterations critical for maximizing their utilization.

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Programming DNA Nanoassemblies into Polyvalent Lysosomal Degraders for Potent Degradation of Pathogenic Membrane Proteins.

Lysosome-targeting chimera (LYTAC) shows great promise for protein-based therapeutics by targeted degradation of disease-associated membrane or extracellular proteins, yet its efficiency is constrained by the limited binding affinity between LYTAC reagents and designated proteins. Here, we established a programmable and multivalent LYTAC system by tandem assembly of DNA into a high-affinity protein degrader, a heterodimer aptamer nanostructure targeting both pathogenic membrane protein and lysosome-targeting receptor (insulin-like growth factor 2 receptor, IGF2R) with adjustable spatial distribution or organization pattern. The DNA-based multivalent LYTACs showed enhanced efficacy in removing immune-checkpoint protein programmable death-ligand 1 (PD-L1) and vascular endothelial growth factor receptor 2 (VEGFR2) in tumor cell membrane that respectively motivated a significant increase in T cell activity and a potent effect on cancer cell growth inhibition. With high programmability and versatility, this multivalent LYTAC system holds considerable promise for realizing protein therapeutics with enhanced activity.

Precision Treatment of Colon Cancer Using Doxorubicin-Loaded Metal-Organic-Framework-Coated Magnetic Nanoparticles.

Due to the limited efficacy and evident side effects of traditional chemotherapy drugs attributed to their lack of specificity and selectivity, novel strategies are essential for improving cancer treatment outcomes. Here, we successfully engineered Fe3O4 magnetic nanoparticles coated with zeolitic imidazolate framework-8 (ZIF-8). The resulting nanocomposite (Fe3O4@ZIF-8) demonstrates efficient adsorption of a substantial amount of doxorubicin (DOX) due to the porous nature of ZIF-8. The drug-loaded nanoparticles, Fe3O4@ZIF-8/DOX, exhibit significant accumulation at the tumor site in SW620 colon-cancer-bearing mice when guided by an external magnetic field. Within the acidic microenvironment of the tumor, the ZIF-8 framework collapses, releasing DOX and effectively inducing tumor cell death, thereby inhibiting cancer progression while not causing undesired side effects, as confirmed by a variety of in vitro and in vivo characterizations. In comparison to free DOX, Fe3O4@ZIF-8/DOX nanoparticles show superior efficacy in colon cancer treatment. Our findings suggest that Fe3O4@ZIF-8 holds promise as a carrier for small-molecule drug adsorption and its ferromagnetic properties provide drug targeting capabilities, thereby enhancing therapeutic effects on tumors at the same drug dosage. With excellent biocompatibility, Fe3O4@ZIF-8 demonstrates potential as a drug carrier in targeted cancer chemotherapy. Our work suggests that a combination of magnetic targeting and acid-responsiveness holds great promise for advancing targeted cancer therapy in precision nanomedicine.

Ligand-free biodegradable poly(beta-amino ester) nanoparticles for targeted systemic delivery of mRNA to the lungs.

Non-viral nanoparticles (NPs) have seen heightened interest as a delivery method for a variety of clinically relevant nucleic acid cargoes in recent years. While much of the focus has been on lipid NPs, non-lipid NPs, including polymeric NPs, have the possibility of improved efficacy, safety, and targeting, especially to non-liver organs following systemic administration. A safe and effective systemic approach for intracellular delivery to the lungs could overcome limitations to intratracheal/intranasal delivery of NPs and improve clinical benefit for a range of diseases including cystic fibrosis. Here, engineered biodegradable poly (beta-amino ester) (PBAE) NPs are shown to facilitate efficient delivery of mRNA to primary human airway epithelial cells from both healthy donors and individuals with cystic fibrosis. Optimized NP formulations made with differentially endcapped PBAEs and systemically administered in vivo lead to high expression of mRNA within the lungs in BALB/c and C57 B/L mice without requiring a complex targeting ligand. High levels of mRNA-based gene editing were achieved in an Ai9 mouse model across bronchial, epithelial, and endothelial cell populations. No toxicity was observed either acutely or over time, including after multiple systemic administrations of the NPs. The non-lipid biodegradable PBAE NPs demonstrate high levels of transfection in both primary human airway epithelial cells and in vivo editing of lung cell types that are targets for numerous life-limiting diseases particularly single gene disorders such as cystic fibrosis and surfactant deficiencies.

Near-infrared hemicyanine photosensitizer for targeted mitochondrial viscosity imaging and efficient photodynamic therapy.

As a severe threat to human health, cancer has always been one of the most significant challenges facing the medical field. However, there is currently no effective technology or method to diagnose and treat cancer simultaneously. Therefore, developing a new approach that integrates diagnosis and treatment holds promise as a means of achieving personalized and precise cancer therapy. In this study, we developed a novel dual-functional near-infrared mitochondrial-targeted photosensitizer, Hcy-I, which is capable of simultaneously monitoring cellular viscosity and specifically targeting mitochondria for photodynamic therapy. Compared with traditional hemicyanine dyes, the introduction of iodine atoms in Hcy-I enhanced spin-orbit coupling (SOC) and promoted the intersystem crossing (ISC) rate, thereby increasing the efficiency of singlet oxygen (1O2) generation. In vitro experiments demonstrated that Hcy-I exhibited high sensitivity to viscosity variations and efficiently generated 1O2 under 638 nm laser irradiation, with an 1O2 quantum yield of up to 48.9 %. Cell experiments further revealed that this photosensitizer could effectively target mitochondria for photodynamic therapy, disrupting mitochondrial membrane potential and inducing cell death. When treated with Hcy-I at a concentration of 0.8 µM, the survival rate of HepG-2 cells was only 13 %. These results suggested that Hcy-I had the potential to integrate cancer diagnosis and treatment. The research not only promotes the development of photodynamic thereby technology, but also opens up new avenues for the diagnosis and treatment of cancer.

Decorating Delivery Vehicles Using Hyaluronic Acid Oligosaccharides Enables Active Targeting Toward Cancer and Minimizes Adverse Effect of Chemotherapeutics.

The major drawback of conventional chemotherapeutic treatment is the non-specificity or inability to ascertain and target cancerous cells directly. In this study, an active targeting strategy that is poised to carry the anticancer agents to the desired sites for therapeutic action while avoiding toxicity to normal organs is provided. The active targeting of delivery vehicles is achieved by ligand-receptor interactions, in particular the specific binding between hyaluronic acid oligosaccharides (oHAs) and CD44 receptors. This study first prepares oHAs by the size-exclusion chromatography and utilizes them to decorate chitosan (CTS) as basic materials (oHAs-CTS) for drug delivery, then fabricates oHAs-CTS into micro/nanoscale carriers to encapsulate agents for cancer chemotherapy. The oHAs-CTS micro/nanocarriers exhibit high drug encapsulation efficiency (58-87%), and the drug releases present a sustained behavior. Notably, oHAs-CTS delivery vehicles display an enhanced active targeting toward cancers and alleviate the cytotoxic effects on normal cells. Additionally, in vivo results show that drug-laden oHAs-CTS nanocarriers demonstrate a significant inhibitory effect on 4 T1 tumors without any toxicity to the major organs. Taken together, the findings highlight the potential of oHAs-CTS micro/nanospheres as delivery vehicles with enhanced active targeted capability toward cancers and minimized adverse effects of chemotherapeutic agents for cancer treatment.

Membrane-camouflaged biomimetic nanoplatform with arsenic complex for synergistic reinforcement of liver cancer therapy.

Aim: Arsenic has excellent anti-advanced liver cancer effects through a variety of pathways, but its severe systemic toxicity forces the need for a safe and effective delivery strategy.Methods: Based on the chelating metal ion properties of polydopamine (PDA), arsenic was immobilized on an organic carrier, and a M1-like macrophage cell membrane (MM)-camouflaged manganese-arsenic complex mesoporous polydopamine (MnAsOx@MP@M) nanoplatform was successfully constructed. MnAsOx@MP@M was evaluated at the cellular level for tumor inhibition and tumor localization, and in vivo for its anti-liver cancer effect in a Hepa1-6 tumor-bearing mouse model.Results: The nanoplatform targeted the tumor site through the natural homing property of MM, completely degraded and released drugs to kill tumor cells in an acidic environment, while playing an immunomodulatory role in promoting tumor-associated macrophages (TAMs) repolarization.Conclusion: MnAsOx@MP@M has synergistically enhanced the targeted therapeutics against liver cancer via nanotechnology and immunotherapy, and it is expected to become a safe and multifunctional treatment platform in clinical oncology.

[Box: see text].

Poly(A) Tail Length of Messenger RNA Regulates Translational Efficiency of the Mitochondria-Targeting Delivery System.

Mitochondria are essential for cellular functions, such as energy production. Human mitochondrial DNA (mtDNA), encoding 13 distinct genes, two rRNA, and 22 tRNA, is crucial for maintaining vital functions, along with nuclear-encoded mitochondrial proteins. However, mtDNA is prone to somatic mutations due to replication errors and reactive oxygen species exposure. These mutations can accumulate, leading to heteroplasmic conditions associated with severe metabolic diseases. Therefore, developing methodologies to improve mitochondrial health is highly demanded. Introducing nucleic acids directly into mitochondria is a promising strategy to control mitochondrial gene expression. Messenger RNA (mRNA) delivery especially offers several advantages such as faster gene expression and reduced risk of genome integration if accidentally delivered to the cell nucleus. In this study, we investigated the effect of the poly(A) tail length of mRNA on the mitochondrial translation to achieve efficient expression. We used a peptide-based mitochondrial targeting system, mitoNEET-(RH)9, comprising a mitochondria-targeting sequence (MTS) and a cationic sequence, to deliver mRNA with various poly(A) tails into the mitochondria. The poly(A) tail length significantly affected translational efficiency, with a medium length of 60 nucleotides maximizing protein expression in various cell lines due to enhanced interaction with mitochondrial RNA-binding proteins. Our findings highlight the importance of optimizing poly(A) tail length for efficient mitochondrial mRNA translation, providing a potential strategy for improving mitochondrial gene therapy. These results pave the way for further exploration of the mechanisms and clinical applications of mitochondrial mRNA delivery systems.

Lysosome-Targeted Bifunctional Therapeutics Induce Autodynamic Cancer Therapy.

Autodynamic cancer therapy possesses tremendous potential for enhancing therapeutic efficacy by initiating the treatment process autonomously within targeted cells. However, challenges related to biocompatibility and targeted delivery have hindered its clinical translation owing to the induction of adverse effects and cytotoxicity in healthy cells. In this study, a novel approach for auto-initiated dynamic therapy by conjugating zwitterionic near-infrared fluorophores to a cell-penetrating peptide is proposed. This enables efficient cellular uptake and specific targeting of therapy to desired cells while avoiding off-target uptake. The zwitterionic bioconjugate causes cancer-specific toxicity following its internalization into the targeted cells, triggered by specific intracellular conditions in lysosomes. This innovative approach enables selective targeting of lysosomes in malignant cells while minimizing cytotoxic effects on normal cells. By targeting lysosomes, the method overcomes inherent risks and side effects associated with conventional cancer treatments, offering a selective and effective approach to cancer therapy.

FDA-approved antivirals ledipasvir and daclatasvir downregulate the Src-EPHA2-Akt oncogenic pathway in colorectal and triple-negative breast cancer cells.

Direct-acting antivirals ledipasvir (LDV) and daclatasvir (DCV) are widely used as part of combination therapies to treat Hepatitis C infections. Here we show that these compounds inhibit the proliferation, invasion, and colony formation of triple-negative MDA-MB-231 breast cancer cells, SRC-transduced SW620 colon cancer cells and SRC- transduced NIH3T3 fibroblasts. DCV also inhibits the expression of PDL-1, which is responsible for resistance to immunotherapy in breast cancer cells. The demonstrated low toxicity in many Hepatitis C patients suggests LDV and DCV could be used in combination therapies for cancer patients. At the molecular level, these direct-acting antivirals inhibit the phosphorylation of Akt and the ephrin type A receptor 2 (EPHA2) by destabilizing a Src-EPHA2 complex, although they do not affect the general kinase activity of Src. Thus, LDV and DCV could be effective drugs for Src-associated cancers without the inherent toxicity of classical Src inhibitors.

The application of bacteria-nanomaterial hybrids in antitumor therapy.

Adverse effects and multidrug resistance remain significant obstacles in conventional cancer therapy. Nanomedicines, with their intrinsic properties such as nano-sized dimensions and tunable surface characteristics, have the potential to mitigate the side effects of traditional cancer treatments. While nanomaterials have been widely applied in cancer treatment, challenges such as low targeting efficiency and poor tumor penetration persist. Recent research has shown that anaerobic bacteria exhibit high selectivity for primary tumors and metastatic cancers, offering good safety and superior tumor penetration capabilities. This suggests that combining nanomaterials with bacteria could complement their respective limitations, opening vast potential applications in cancer therapy. The use of bacteria in combination with nanomaterials for anticancer treatments, including chemotherapy, radiotherapy, and photothermal/photodynamic therapy, has contributed to the rapid development of the field of bacterial oncology treatments. This review explores the mechanisms of bacterial tumor targeting and summarizes strategies for synthesizing bacterial-nanomaterial and their application in cancer therapy. The combination of bacterial-nanomaterial hybrids with modern therapeutic approaches represents a promising avenue for future cancer treatment research, with the potential to improve treatment outcomes for cancer patients.