Tumor-homing Ability Research Articles

A Novel Oncolytic Virus Formulation Based on Mesenchymal Stem Cell-Derived Vesicles for Tumor Therapy.

Developing new drug delivery systems is crucial for enhancing the efficacy of oncolytic virus (OV) therapies in cancer treatment. In this study, mesenchymal stem cell (MSC)-derived vesicles and oncolytic viruses are exploited to construct a novel formulation. It has been hypothesized that vesicle-coated OVs could amplify cytotoxic effects through superior internalization by tumor cells. MSC vesicles possess natural tumor homing ability and biocompatibility, which can enhance the targeting, uptake, and therapeutic effects of OVs on tumor cells. Experimental results indicated that this treatment system has increased the apoptosis of tumor cells. Furthermore, flow cytometry analysis demonstrated that the uptake of tumor cells by OVs coated with MSC vesicles soared away compared to uncoated OVs, being 1.5 times than that of the uncoated group. Additionally, the confocal laser scanning microscopy also showed that the fluorescence intensity within tumor cells pretreated with MSC-coated OVs was greater. Meanwhile, propidium iodide (PI) staining revealed that MSC-coated Ovs exposed to tumor cells accelerating the apoptosis of the latter. According to the statistics, the number of dead cells was increased, and the flow cytometry testified that the apoptosis in the MSC-coated OV group was as high as 23.78%. These findings highlight the potential of MSC vesicle-coated OVs in enhancing the delivery and efficacy of oncolytic virus therapy, providing a promising strategy for cancer treatment.

Macrophage membrane-camouflaged pure-drug nanomedicine for synergistic chemo- and interstitial photodynamic therapy against glioblastoma.

Glioblastoma (GBM) persists as a highly fatal malignancy, with current clinical treatments showing minimal progress over years. Interstitial photodynamic therapy (iPDT) holds promise due to its minimally invasive nature and low toxicity but is impeded by poor photosensitizer penetration and inadequate GBM targeting. Here, we developed a biomimetic pure-drug nanomedicine (MM@CT), which co-assembles the photosensitizer chlorin e6 (Ce6) and the first-line chemotherapeutic drug (temozolomide, TMZ) for GBM, then camouflaged with macrophage membranes. This design eliminates the need for traditional excipients, ensuring formulation safety and achieving exceptionally high drug loading with 73.2 %. By leveraging the biomimetic properties of macrophage membranes, MM@CT evades clearance by the mononuclear phagocyte system and can overcome blood circulatory barriers to target intracranial GBM tumors due to its inherent tumor-homing ability. Consequently, this targeted strategy enables precise delivery of TMZ to the tumor site while significantly enhancing Ce6 accumulation within the tumor tissue. Upon intra-tumoral irradiation using an optical fiber, activated Ce6 synergizes with TMZ to exert both cytotoxic effects from chemotherapy and unique advantages from iPDT simultaneously attacking GBM tumors in a dual manner. In subcutaneous and intracranial GBM mouse models, MM@CT exhibits remarkable anti-tumor efficacy with minimal systemic toxicity, emerging as a promising GBM treatment strategy. STATEMENT OF SIGNIFICANCE: Glioblastoma (GBM) remains a formidable brain cancer, posing significant therapeutic challenges due to the presence of the blood-brain barrier (BBB) and tumor heterogeneity. To overcome these obstacles, we have developed MM@CT, a biomimetic nanomedicine with exceptional drug loading efficiency of 73.2 %. MM@CT incorporates the photosensitizer Ce6 and chemotherapy agent TMZ, encapsulated within nanoparticles and camouflaged with macrophage membranes. This innovative design enables efficient BBB penetration, precise tumor targeting, and synergistic application of chemotherapy and photodynamic therapy. Encouragingly, preclinical evaluations have demonstrated substantial antitumor activity with minimal systemic toxicity, positioning MM@CT as a promising therapeutic strategy for GBM.

Mesenchymal stem cells - the secret agents of cancer immunotherapy: Promises, challenges, and surprising twists.

Mesenchymal stem cells (MSCs) are recognized for their immunomodulatory capabilities, tumor-homing abilities, and capacity to serve as carriers for therapeutic agents. This review delves into the role of adoptively transferred MSCs in tumor progression, their interactions with the tumor microenvironment, and their use in delivering anti-cancer drugs, oncolytic viruses, and genetic material. It also addresses the challenges and limitations associated with MSC therapy, such as variability in MSC preparations and potential tumorigenic effects emphasizing the need for advanced genetic engineering and personalized approaches to enhance therapeutic efficacy. The review concludes with an optimistic outlook on the future of MSC-based therapies, underscoring their promise to develop effective and personalized cancer treatments.

Optimized protocol for the isolation and expansion of menstrual blood-derived mesenchymal stem cells for combination with oncolytic adenoviruses in cancer treatment

Oncolytic viruses (OVs) are a promising therapeutic approach for cancer, although their systemic administration faces significant challenges. Mesenchymal stem cells have emerged as potential carriers to overcome these obstacles due to their tumor-tropic properties. This study investigates the use of menstrual blood-derived mesenchymal stem cells (MenSCs) as carriers for oncolytic viruses in cancer therapy, focusing on enhancing their efficacy through different culture conditions. MenSCs were isolated from donors of different ages and cultured under normoxic and hypoxic conditions, with varying adherence capacities. Hypoxic conditions significantly improved MenSCs proliferation and tumor migration capabilities, as demonstrated by proliferation assays and RNA-Seq analysis, which revealed upregulation of genes related to cell division and tumor tropism. In vivo studies using a lung adenocarcinoma mouse model confirmed that hypoxia-conditioned MenSCs had superior tumor homing abilities. The study also demonstrated the feasibility of establishing a master and working cell bank from a single menstrual blood donation. These findings suggest that hypoxia-conditioned MenSCs could be highly effective as OV carriers, potentially leading to better clinical outcomes in cancer treatment by enhancing tumor targeting and therapeutic efficacy.

Synergistic Enhancement of Photodynamic Cancer Therapy with Mesenchymal Stem Cells and Theranostic Nanoparticles.

Nanoparticles engineered to combat cancer and other life-threatening diseases may significantly improve patient outcomes. However, inefficient nanoparticle delivery to tumors limits their use and necessitates the development of complex delivery approaches. Here, we examine this issue by harnessing the tumor-homing abilities of human mesenchymal stem cells (MSCs) to deliver a decoupled theranostic complex of rare earth-doped nanoparticles (dNPs) and photosensitizer chlorin e6 (Ce6) to tumors. We show that both bone-marrow- and skin-derived MSCs can transport the dNP-Ce6 complex inside tumor spheroids, which is challenging to accomplish by passive delivery alone. MSCs deliver the dNP-Ce6 complex across the tumor spheroid, facilitating more effective photodynamic damage and tumor destruction than passively accumulated dNP-Ce6. The dNP-Ce6 complex also provides the built-in ability to monitor the MSC migration without causing undesired phototoxicity, which is essential for maximal and side-effect-free delivery of nanoparticles. Our results demonstrate how MSCs can be used as delivery vehicles for the transportation of the dNP-Ce6 complex, addressing the limitations of passive nanoparticle delivery and providing light-based theranostics.

A Comparison of in vivo Tumor-Homing Abilities of Placental-Derived and Bone Marrow-Derived Mesenchymal Stromal Cells in High-Risk Neuroblastoma

BackgroundNeuroblastoma is a highly lethal malignancy of young children. Mesenchymal stromal cells (MSCs) may represent a novel cellular delivery vehicle due to their innate tumor-homing properties. We compared in vivo homing abilities of placental-derived MSCs (PMSCs) and bone marrow-derived MSCs (BM-MSCs) in an orthotopic neuroblastoma xenograft. Methods28 mice underwent direct implantation of neuroblastoma cells (cell line NB1643) into the adrenal gland followed by intraperitoneal injection of 5 × 106 MSCs (PMSC n = 13, BM-MSC n = 13, PBS controls n = 2). MSC migration was monitored with in vivo imaging system (IVIS) radiance measurements at multiple timepoints post-MSC injection. Necropsy timepoints were 72 h (n = 10) and 7 days (n = 16). Ex vivo imaging was performed on all adrenal masses and select organ tissues. Immunohistochemistry (IHC) assessed the presence of MSCs in tumors. ResultsIVIS demonstrated initial diffuse signal that migrated to the left abdomen. Radiance decreased over time, but MSC signal persisted at day 7 in all animals. Ex vivo IVIS demonstrated signal in the adrenal tumor but not other organs. There was no significant difference in average ex vivo adrenal mass radiance between MSC groups (p = 0.74). IHC confirmed presence of both MSC types within the tumor. ConclusionPMSCs and BM-MSCs successfully migrated to neuroblastoma tumor tissues in vivo without evidence of migration to other organs. MSCs migrate within 72 h and persisted within the tumor up to 7 days. There was no significant difference in homing capabilities of PMSCs compared to BM-MSCs, indicating that either cell type has potential as a drug delivery vehicle. Type of studyOriginal Research. Level of Evidencen/a.

In situ customized apolipoprotein B48-enriched protein corona enhances oral gene delivery of chitosan-based nanoparticles

The formation of protein corona (PC) is important for promoting the in vivo delivery of nanoparticles (NPs). However, PC formed in the physiological environment of oral delivery is poorly understood. Here, we engineered seven types of trimethyl chitosan–cysteine (TC) NPs, with distinct molecular weights, quaternization degrees, and thiolation degrees, to deeply investigate the influence of various PC formed in the physiological environment of oral delivery on in vivo gene delivery of polymeric NPs, further constructing the relationship between the surface characteristics of NPs and the efficacy of oral gene delivery. Our findings reveal that TC7 NPs, with high molecular weight, moderate quaternization, and high sulfhydryl content, modulate PC formation in the gastrointestinal tract, thereby reducing particle size and promoting oral delivery of gene loaded TC7 NPs. Orally delivered TC7 NPs target macrophages by in situ adsorption of apolipoprotein (Apo) B48 in intestinal tissue, leading to the improved in vivo antihepatoma efficacy via the natural tumor homing ability of macrophages. Our results suggest that efficient oral delivery of genes can be achieved through an in situ customized ApoB48-enriched PC, offering a promising modality in treating macrophage-related diseases.

Current Strategies and Therapeutic Applications of Mesenchymal Stem Cell-Based Drug Delivery.

Mesenchymal stem cells (MSCs) have emerged as a promising approach for drug delivery strategies because of their unique properties. These strategies include stem cell membrane-coated nanoparticles, stem cell-derived extracellular vesicles, immunomodulatory effects, stem cell-laden scaffolds, and scaffold-free stem cell sheets. MSCs offer advantages such as low immunogenicity, homing ability, and tumor tropism, making them ideal for targeted drug delivery systems. Stem cell-derived extracellular vesicles have gained attention for their immune properties and tumor-homing abilities, presenting a potential solution for drug delivery challenges. The relationship between MSC-based drug delivery and the self-renewal and differentiation capabilities of MSCs lies in the potential of engineered MSCs to serve as effective carriers for therapeutic agents while maintaining their intrinsic properties. MSCs exhibit potent immunosuppressive functions in MSC-based drug delivery strategies. Stem cell-derived EVs have low immunogenicity and strong therapeutic potential for tissue repair and regeneration. Scaffold-free stem cell sheets represent a cutting-edge approach in regenerative medicine, offering a versatile platform for tissue engineering and regeneration across different medical specialties. MSCs have shown great potential for clinical applications in regenerative medicine because of their ability to differentiate into various cell types, secrete bioactive factors, and modulate immune responses. Researchers are exploring these innovative approaches to enhance drug delivery efficiency and effectiveness in treating various diseases.

Self-Generating Gold Nanocatalysts in Autologous Tumor Cells for Targeted Catalytic Immunotherapy.

Employing tumor whole cells for tumor immunotherapy is a promising tumor therapy proposed in the early stage, but its therapeutic efficacy is weakened by the methods of eliminating pathogenicity and the mass ratio of the effective antigen carried by itself. Here, by adding gold ion to live cancer cells in the microfluidic droplets, this work obtains dead tumor whole cells with NIR-controlled catalytic ability whose pathogenicity is removed while plenary tumor antigens, major structure, and homing ability are reserved. The engineered tumor cell (Cell-Au) with the addition of prodrug provides 1O2 in an O2-free Russell mechanism, which serves better in a hypoxic tumor microenvironment. This tumor whole-cell catalytic vaccine (TWCV) promotes the activation of dendritic cells and the transformation of macrophages into tumor suppressor phenotype. In 4T1 tumor-bearing mice, the Cell-Au-based vaccine supports the polarization of cytotoxicity T cells, resulting in tumor eradication and long-term animal survival. Compared with antigen vaccines or adoptive cell therapy which takes months to obtain, this TWCV can be prepared in just a few days with satisfactory immune activation and tumor therapeutic efficacy, which provides an alternative way for the preparation of personalized tumor vaccines across tumor types and gives immunotherapy a new path.

Biomimetic engineered nanoparticles target drug-resistant tumor cells and heterogeneous blood vessels for combination therapy of osteosarcoma

Given that the treatment of drug-resistant osteosarcoma is a significant clinical challenge, in drug-resistant tumors, the role of endothelial cells has been recently emphasized. We noted that heterogeneous vascular endothelial cells (ONHVECs) in drug-resistant osteosarcoma tissues may inhibit macrophage-mediated killing of tumor cells, thus promoting the occurrence of drug resistance. Accordingly, we designed a type of hybrid membrane-coated multifunctional nanoparticle (NP), SiO2@PDA/Fe3+@Cis@HM. The NPs had good biocompatibility and enhanced the occurrence of low-temperature photothermal Fenton-like reactions. The hybrid membrane endowed the NPs with a tumor homing ability and homologous cell targeting ability, thus simultaneously targeting drug-resistant tumor cells and ONHVECs, in addition to killing tumor cells via efficient delivery of cisplatin and ROS produced by accelerated Fenton-like reactions. Through in vivo and in vitro experiments, we confirmed that SiO2@PDA/Fe3+@Cis@HM NPs efficiently killed tumor cells as well as ONHVECs. The endogenous exosomes produced by damaged ONHVECs induced anti-tumor M1 macrophage polarization to indirectly kill tumor cells and achieve synergistic therapy. This immune regulation was completely inherent and exhibited consistent efficacy, without ethical connotations. In conclusion, this multifunctional treatment strategy is the first to adopt a tumor cell/vascular endothelial cell double-targeted concept, which realized the direct killing of drug-resistant tumor cells and a natural immune enhancement response and could become a new paradigm for the treatment of drug-resistant osteosarcoma.

The potential applications of artificially modified exosomes derived from mesenchymal stem cells in tumor therapy.

Mesenchymal stem cells (MSCs) have tumor-homing ability and play critical roles in tumor treatment, but their dual influences on tumor progression limit their therapeutic applications. Exosomes derived from MSCs (MSC-exosomes) exhibit great potential in targeted tumor treatment due to their advantages of high stability, low immunogenicity, good biocompatibility, long circulation time and homing characteristics. Furthermore, the artificial modification of MSC-exosomes could amplify their advantages and their inhibitory effect on tumors and could overcome the limit of tumor-promoting effect. In this review, we summarize the latest therapeutic strategies involving artificially modified MSC-exosomes in tumor treatment, including employing these exosomes as nanomaterials to carry noncoding RNAs or their inhibitors and anticancer drugs, and genetic engineering modification of MSC-exosomes. We also discuss the feasibility of utilizing artificially modified MSC-exosomes as an emerging cell-free method for tumor treatment and related challenges.

Cell-nanocarrier drug delivery system: a promising strategy for cancer therapy.

Tumor targeting has been a great challenge for drug delivery systems. A number of nanotechnology-derived drug carriers have been developed for cancer treatment to improve efficacy and biocompatibility. Among them, the emergence of cell-nanocarriers has attracted great attention, which simulates cell function and has good biocompatibility. They can also escape the clearance of reticuloendothelial system, showing a long-cycle effect. The inherent tumor migration and tumor homing ability of cells increase their significance as tumor-targeting vectors. In this review, we focus on the combination of stem cells, immune cells, red blood cells, and cell membranes to nanocarriers, which enable chemotherapy agents to efficiently target lesion sites and improve drug distribution while being low toxic and safe. In addition, we discuss the pros and cons of these nanoparticles as well as the challenges and opportunities that lie ahead. Although research to address these limitations is still ongoing, this promising tumor-targeted drug delivery system will provide a safe and effective platform against cancer.

Immune cell membrane-based biomimetic nanomedicine for treating cancer metastasis.

Metastasis is the leading cause of cancer-related death. Despite extensive treatment, the prognosis for patients with metastatic cancer remains poor. In addition to conventional surgical resection, radiotherapy, immunotherapy, chemotherapy, and targeted therapy, various nanobiomaterials have attracted attention for their enhanced antitumor performance and low off-target effects. However, nanomedicines exhibit certain limitations in clinical applications, such as rapid clearance from the body, low biological stability, and poor targeting ability. Biomimetic methods utilize the natural biomembrane to mimic or hybridize nanoparticles and circumvent some of these limitations. Considering the involvement of immune cells in the tumor microenvironment of the metastatic cascade, biomimetic methods using immune cell membranes have been proposed with unique tumor-homing ability and high biocompatibility. In this review, we explore the impact of immune cells on various processes of tumor metastasis. Furthermore, we summarize the synthesis and applications of immune cell membrane-based nanocarriers increasing therapeutic efficacy against cancer metastases via immune evasion, prolonged circulation, enhanced tumor accumulation, and immunosuppression of the tumor microenvironment. Moreover, we describe the prospects and existing challenges in clinical translation.

CD4-/CD8- double-negative tumor-infiltrating lymphocytes expanded from solid tumor tissue suppress the proliferation of tumor cells in an MHC-independent way.

Tumor-infiltrating lymphocytes (TILs) have shown remarkable clinical responses in some patients with advanced solid tumors. As a rare subset of TILs, CD4-/CD8- double-negative T cells (DNTs) were poorly known. This study aims to investigate the characteristics and function of CD3+CD4-CD8- TILs (double-negative TIL, DN-TILs) derived from solid tumor. DN-TILs were derived and expanded ex vivo from resected gastric carcinoma tissue and phenotyped by flow cytometry. The cytotoxicity of DN-TILs was determined against established tumor cell lines in vitro or through in vivo adoptive transfer into xenograft models. K562 cells were transferred with the HLA gene to verify whether the cytotoxicity of DN-TILs was MHC-independent. Flow cytometric analysis revealed a high-purity population of DN-TILs (> 97%) within CD3+ TILs, which expanded more than 800-folds in 2weeks, consisting of a mixture of alpha-beta (αβ) and gamma-delta (γδ) T-cell receptor (TCR)-expressing cells (with the majority being αβ-TCR, > 95%). Using single-cell RNA sequencing, the expanded DN-TILs were categorized into four main subsets, Natural Killer T cells (approximately 80%, 5563 in 7028), Progenitor cells, Germ cells and T helper2 cells. DN-TILs exhibited a broad anticancer cytotoxicity in a donor-unrestricted manner against various cancer cell lines derived from pancreatic cancer (Panc-1), gastric cancer (HGC-27), ovarian cancer (SKOV-3), malignant melanoma (A375). The cytotoxicity was MHC-independent, which was not altered in K562 transferring with HLA gene or not. DN-TILs significantly reduced tumor volume in xenograft models with superior tumor-homing ability and low off-target toxicity. Gastric carcinoma derived DN-TIL can target tumor cells in vitro and in vivo. DN-TILs have the potential to be used as a adoptive cell therapy for solid cancers with both the advantages of DNT and TIL.

Multifunctional gold nanorods in low-temperature photothermal interactions for combined tumor starvation and RNA interference therapy.

Collateral damage to healthy tissue, uneven heat distribution, inflammatory diseases, and tumor metastasis induction hinder the translation of high-temperature photothermal therapy (PTT) from bench to practical clinical applications. In this report, a multifunctional gold nanorod (GNR)-based nanosystem was designed by attaching siRNA against B7-H3 (B7-H3si), glucose oxidase (GOx), and hyaluronic acid (HA) for efficient low-temperature PTT. Herein, GOx can not only exhaust glucose to induce starvation therapy but also reduce the heat shock protein (HSP), realizing the ablation of tumors without damage to healthy tissues. Evidence shows that B7-H3, a type I transmembrane glycoprotein molecule, plays essential roles in growth, metastasis, and drug resistance. By initiating the downregulation of B7-H3 by siRNA, siRNA-GOx/GNR@HA NPs may promote the effectiveness of treatment. By targeting cluster of differentiation 44 (CD44) and depleting B7-H3 and HSPs sequentially, siRNA-GOx/GNR@HA NPs showed 12.9-fold higher lung distribution than siRNA-GOx/GNR NPs. Furthermore, 50% of A549-bearing mice in the siRNA-GOx/GNR NPs group survived over 50 days. Overall, this low-temperature phototherapeutic nanosystem provides an appropriate strategy for eliminating cancer with high treatment effectiveness and minimal systemic toxicity. STATEMENT OF SIGNIFICANCE: To realize efficient tumor ablation under mild low-temperature (42-45℃) and RNA interference simultaneously, here we developed a multifunctional gold nanorod (GNR)-based nanosystem (siRNA-GOx/GNR@HA NPs). This nanoplatform can significantly inhibit tumor cell proliferation and induce cell apoptosis by downregulation of HSP90α, HSP70, B7-H3, p-AKT, and p-ERK and upregulation of cleaved caspase-9 at mild low-temperature due to its superior tumor homing ability and the combined effect of photothermal effect, glucose deprivation-initiated tumor starvation, and B7-H3 gene silence effect. It is believed that this multifunctional low-temperature photothermal nanosystem with efficient and specific anticancer properties, shows a potential application in clinical tumor treatment.

Extracellular vesicles derived from dental mesenchymal stem/stromal cells with gemcitabine as a cargo have an inhibitory effect on the growth of pancreatic carcinoma cell lines in vitro

Extracellular vesicles (EVs) are nowadays a target of interest in cancer therapy as a successful drug delivering tool. Based on their many beneficial biocompatible properties are designed to transport nucleic acids, proteins, various nanomaterials or chemotherapeutics. Extracellular vesicles derived from mesenchymal stem/stromal cells (MSCs) possess their tumor-homing abilities. This inspired us to engineer the MSC's EVs to be packed with chemotherapeutic agents and deliver it as a Trojan horse directly into tumor cells. In our study, human dental pulp MSCs (DP-MSCs) were cultivated with gemcitabine (GCB), which led to its absorption by the cells and subsequent secretion of the drug out into conditioned media in EVs. Concentrated conditioned media containing small EVs (potentially exosomes) significantly inhibited the cell growth of pancreatic carcinoma cell lines in vitro. DP-MSCs were simultaneously engineered to express a suicide gene fused yeast cytosinedeaminase:uracilphosphoribosyltransferase (yCD::UPRT). The product of the suicide gene converts non-toxic prodrug 5-fluorocytosine (5-FC) to highly cytotoxic chemotherapeutic drug 5-fluorouracil (5-FU) in the recipient cancer cells. Conversion of 5-FC to 5-FU had an additional effect on cancer cell's growth inhibition. Our results showed a therapeutic potential for DP-MSC-EVs to be designed for successful delivering of chemotherapeutic drugs, together with prodrug suicide gene therapy system.

Synergistic treatment of osteosarcoma with biomimetic nanoparticles transporting doxorubicin and siRNA.

Osteosarcoma tumors are the most common malignant bone tumors in children and adolescents. Their treatment usually requires surgical removal of all detectable cancerous tissue and multidrug chemotherapy; however, the prognosis for patients with unresectable or recurrent osteosarcoma is unfavorable. To make chemotherapy safer and more effective for osteosarcoma patients, biomimetic nanoparticles (NPs) camouflaged by mesenchymal stem cell membranes (MSCMs) were synthesized to induce osteosarcoma cell apoptosis by co-delivering the anticancer drug doxorubicin hydrochloride(DOX) and a small interfering RNA (siRNA). Importantly, these NPs have high biocompatibility and tumor-homing ability. This study aimed to improve the efficacy of osteosarcoma therapy by using the synergistic combination of DOX and an siRNA targeting the apoptosis suppressor gene survivin. Biomimetic NPs (DOX/siSUR-PLGA@MSCM NPs) were synthesized by coloading DOX and survivin siRNA (siSUR) into poly (lactide-co-glycolide acid) (PLGA) via a double-emulsion solvent evaporation method. The NPs were camouflaged by MSCMs to deliver both DOX and survivin-targeting siRNA and characterized and evaluated in terms of cellular uptake, in vitro release, in vitro and in vivo antitumor effects, and biosafety. DOX/siSUR-PLGA@MSCM NPs had good tumor-homing ability due to the MSCMs modification. The drug-laden biomimetic NPs had good antitumor effects in homozygous MG63 tumor-bearing mice due to the synergistic effect of the drug combination. DOX/siSUR-PLGA@MSCM NPs can show improved therapeutic effects in osteosarcoma patients due to the combination of a chemotherapeutic drug and gene therapy based on their good tumor targeting and biosafety.

Magnetotactic Bacteria-Based Drug-Loaded Micromotors for Highly Efficient Magnetic and Biological Double-Targeted Tumor Therapy.

Bacteria-mediated cancer therapy has attracted much attention in recent years. However, using magnetotactic bacteria as both a drug carrier and a drug for cancer therapy has never been reported. Herein, we incorporated a photosensitizer chlorin e6 (Ce6) into the M. magneticum strain AMB-1 through a chemical bond or physical blending. A chemical reaction was finally selected for fabricating AMB-1/Ce6 micromotors, as such micromotors exhibited high drug payload and normal bacterial activities. An interesting finding is that AMB-1 is not only an excellent drug carrier but also a unique drug that could inhibit mouse tumor growth. We also, for the first time, demonstrated that AMB-1 is a photosensitizer. Under laser irradiation, micromotors killed cancer cells with high efficiency due to the high-level reactive oxygen species generated by the micromotors. Micromotors could target the hypoxic and normoxic regions in vitro via both the active swimming of AMB-1 and external magnetic field guidance. Micromotors showed high tumor-homing ability owing to the above double targeting mechanisms. After injection with the micromotors followed by magnetic field guidance and laser irradiation, the growth of mouse tumors was significantly inhibited owing to the AMB-1-based biotherapy and phototoxicity of AMB-1 and Ce6. This micromotor-mediated tumor-targeted therapy strategy may be a great platform for treating many types of solid tumors.

Current Situation and Prospect of Adoptive Cellular Immunotherapy for Malignancies.

Adoptive cell immunotherapy (ACT) is an innovative promising treatment for tumors. ACT is characterized by the infusion of active anti-tumor immune cells (specific and non-specific) into patients to kill tumor cells either directly or indirectly by stimulating the body's immune system. The patient's (autologous) or a donor's (allogeneic) immune cells are used to improve immune function. Chimeric antigen receptor (CAR) T cells (CAR-T) is a type of ACT that has gained attention. T cells from the peripheral blood are genetically engineered to express CARs that rapidly proliferate and specifically recognize target antigens to exert its anti-tumor effects. Clinical application of CAR-T therapy for hematological tumors has shown good results, but adverse reactions and recurrence limit its applicability. Tumor infiltrating lymphocyte (TIL) therapy is effective for solid tumors. TIL therapy exhibits T cell receptor (TCR) clonality, superior tumor homing ability, and low targeted toxicity, but its successful application is limited to a number of tumors. Regardless, TIL and CAR-T therapies are effective for treating cancer. Additionally, CAR-natural killer (NK), CAR-macrophages (M), and TCR-T therapies are currently being researched. In this review, we highlight the current developments and limitations of several types of ACT.

Fucoidan-based dual-targeting mesoporous polydopamine for enhanced MRI-guided chemo-photothermal therapy of HCC via P-selectin-mediated drug delivery

The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma (HCC). Here, a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin (FMPDA/Gd3+/DOX) was prepared as an effective theranostic agent for magnetic resonance imaging (MRI)-guided chemo-photothermal therapy of HCC. It was found that FMPDA/Gd3+/DOX had a high photothermal conversion efficiency of 33.4% and excellent T1−MRI performance with a longitudinal relaxivity (r1) value of 14.966 mM−1·s − 1. Moreover, the results suggested that FMPDA/Gd3+/DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells, which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors. The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd3+/DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality. Overall, our study demonstrated that FMPDA/Gd3+/DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics