Targeting the Gastrin-Releasing Peptide Receptor (GRP-R) in Cancer Therapy: Development of Bombesin-Based Peptide-Drug Conjugates.

Targeted tumour therapy has proved to be an efficient alternative to overcome the limitations of conventional chemotherapy. Among several receptors upregulated in cancer cells, the gastrin-releasing peptide receptor (GRP-R) has recently emerged as a promising target for cancer imaging, diagnosing and treatment due to its overexpression on cancerous tissues such as breast, prostate, pancreatic and small-cell lung cancer. Herein, we report on the in vitro and in vivo selective delivery of the cytotoxic drug daunorubicin to prostate and breast cancer, by targeting GRP-R. Exploiting many bombesin analogues as homing peptides, including a newly developed peptide, we produced eleven daunorubicin-containing peptide-drug conjugates (PDCs), acting as drug delivery systems to safely reach the tumour environment. Two of our bioconjugates revealed remarkable anti-proliferative activity, an efficient uptake by all three tested human breast and prostate cancer cell lines, high stability in plasma and a prompt release of the drug-containing metabolite by lysosomal enzymes. Moreover, they revealed a safe profile and a consistent reduction of the tumour volume in vivo. In conclusion, we highlight the importance of GRP-R binding PDCs in targeted cancer therapy, with the possibility of further tailoring and optimisation.

SERPINA5 promotes tumour cell proliferation by modulating the PI3K/AKT/mTOR signalling pathway in gastric cancer.

SERPINA5 belongs to the serine protease inhibitor superfamily and has been reported to be lowly expressed in a variety of malignancies. However, few report of SERPINA5 in gastric cancer has been found. The purpose of this study was to determine the role of SERPINA5 in GC and to investigate potential tumorigenic mechanisms. We performed qPCR to determine the level of SERPINA5 expression in GC. We used public databases to evaluate whether SERPINA5 could be utilized to predict overall survival and disease-free survival in GC patients. We also knocked down the expression of SERPINA5 and evaluated its effect on cell proliferation and migration. Furthermore, we explored the signal pathways and regulatory mechanisms related to SERPINA5 functions. According to our findings, SERPINA5 was shown to exhibit high expression in GC. Notably, SERPINA5 was prognostic in GC with high expression being unfavourable. SERPINA5 was further observed to promote GC tumorigenesis by modulating GC cell proliferation ability. Mechanically, SERPINA5 could inhibit CBL to regulate the PI3K/AKT/mTOR signalling pathway, thereby promoting GC carcinogenesis progression. These results highlight the important role of SERPINA5 in GC cell proliferation and suggest that SERPINA5 could be a novel target for GC treatment and a predictor for GC prognosis.

A "Self-Checking" pH/Viscosity-Activatable NIR-II Molecule for Real-Time Evaluation of Photothermal Therapy Efficacy.

We present a second near-infrared (NIR-II) self-checking molecule, LET-1052, for acidic tumor microenvironment (TME) turn-on photothermal therapy (PTT), followed by viscosity based therapeutic efficacy evaluation by itself in two independent channels, denoted as "self-checking" strategy. In acidic TME, LET-1052 was protonated and turned on NIR-II absorption for PTT under 1064 nm laser irradiation. Subsequently, PTT-induced cellular death increases intracellular viscosity, which inhibited the intramolecular rotation of LET-1052, resulting in the enhancement of NIR-I fluorescence for real-time evaluation of PTT efficacy. After PTT of tumor-bearing mice for different periods of NIR-II laser irradiation, NIR-I fluorescence in the tumor region showed positive correlation with tumor growth inhibition rate, demonstrating reliable and prompt prediction of PTT efficacy. The strategy may be expanded for instant evaluation of other therapeutic modalities for personalized medicine.

Therapy for advanced cholangiocarcinoma: Current knowledge and future potential.

Cholangiocarcinoma (CCA) is a biliary epithelial tumour that can emerge at any point in the biliary tree. It is commonly classified based on its anatomical site of development into intrahepatic cholangiocarcinoma (ICC), perihilar cholangiocarcinoma (PCC) and distal cholangiocarcinoma (DCC), each of which is associated with varying patient demographics, molecular characteristics and treatment options. CCA patients have poor overall prognoses and 5-year survival rates. Additionally, CCA is often diagnosed at an advanced stage, with surgical treatment restricted to early-stage disease. Owing to an increase in the incidence of ICC, that of CCA is also on the rise, with a corresponding increase in the associated mortality, particularly in South America and Asia. Therefore, the development of an effective treatment is crucial to improve the survival of CCA patients. We aimed to systematically review the current understanding of advanced CCA treatment and discuss potential effective strategies.

Interaction between intestinal microbiota and tumour immunity in the tumour microenvironment.

In recent years, an increasing number of studies have reported that intestinal microbiota have an important effect on tumour immunity by affecting the tumour microenvironment (TME). The intestinal microbiota are closely associated with various immune cells, such as T lymphocytes, natural killer cells (NK cells) and macrophages. Some bacteria, such as Akkermansia muciniphila (A. muciniphila) and Lactobacillus reuteri (L. reuteri), have been shown to improve the effect of tumour immunity. Furthermore, microbial imbalance, such as the increased abundance of Fusobacterium nucleatum (F. nucleatum) and Helicobacter hepaticus (H. hepaticus), generally causes tumour formation and progression. In addition, some microbiota also play important roles in tumour immunotherapy, especially PD-L1-related therapies. Therefore, what is the relationship between these processes and how do they affect each other? In this review, we summarize the interactions and corresponding mechanisms among the intestinal microbiota, immune system and TME to facilitate the research and development of new targeted drugs and provide new approaches to tumour therapy.

Human cytomegalovirus DNA detection in a recurrent glioblastoma multiforme tumour, but not in whole blood: a case report and discussion about the HCMV latency and therapy perspectives.

In the current study, a 58-year-old male patient presented with recurrent glioblastoma multiforme (GBM). The patient underwent surgical resection, 4 months earlier, followed by radiotherapy and chemotherapy. During the second surgical intervention, tumour tissue and whole blood were sampled and analysed for human cytomegalovirus (HCMV) DNA, immediate early (IE) mRNA and pp65 mRNA. HCMV DNA was detected only in the recurrent tumour tissue but not in the whole blood. Neither IE mRNA nor pp65 mRNA was expressed. Our result suggests HCMV latency in the brain tumour with detectable level of viral DNA. More data are needed to understand the HCMV infection chronology in the brain tumours but our data could be important for further studies of HCMV antigens on the tumour surface and anti-GBM therapy.

Multiparametric MR for non-invasive evaluation of tumour tissue histological characteristics after radionuclide therapy.

Early non-invasive tumour therapy response assessment requires methods sensitive to biological and physiological tumour characteristics. The aim of this study was to find and evaluate magnetic resonance imaging (MRI) derived tumour tissue parameters that correlate with histological parameters and that reflect effects of radionuclide therapy. Mice bearing a subcutaneous human small-intestine neuroendocrine tumour were i.v. injected with 177 Lu-octreotate. MRI was performed (7 T Bruker Biospec) on different post-therapy intervals (1 and 13 days) using T2-weighted imaging, mapping of T2* and T1 relaxation time constants, as well as diffusion and dynamic contrast enhancement (DCE-MRI) techniques. After MRI, animals were killed and tumours excised. Four differently stained histological sections of the most central imaged tumour plane were digitized, and segmentation techniques were used to produce maps reflecting fibrotic and vascular density, apoptosis, and proliferation. Histological maps were aligned with MRI-derived parametric maps using landmark-based registration. Correlations and predictive power were evaluated using linear mixed-effects models and cross-validation, respectively. Several MR parameters showed statistically significant correlations with histological parameters. In particular, three DCE-MRI-derived parameters reflecting capillary function additionally showed high predictive power regarding apoptosis (2/3) and proliferation (1/3). T1 could be used to predict vascular density, and perfusion fraction derived from diffusion MRI could predict fibrotic density, although with lower predictive power. This work demonstrates the potential to use multiparametric MRI to retrieve important information on the tumour microenvironment after radiotherapy. The non-invasiveness of the method also allows longitudinal tumour tissue characterization. Further investigation is warranted to evaluate the parameters highlighted in this study longitudinally, in larger studies, and with additional histological methods.

Gadolinium-doped iron oxide nanoparticles induced magnetic field hyperthermia combined with radiotherapy increases tumour response by vascular disruption and improved oxygenation.

The gadolinium-doped iron oxide nanoparticles (GdIONP) with greater specific power adsorption rate (SAR) than Fe3O4 was developed and its potential application in tumour therapy and particle tracking were demonstrated in transgenic adenocarcinoma of the mouse prostate C1 (TRAMP-C1) tumours. The GdIONPs accumulated in tumour region during the treatment could be clearly tracked and quantified by T2-weighted MR imaging. The therapeutic effects of GdIONP-mediated hyperthermia alone or in combination with radiotherapy (RT) were also evaluated. A significant increase in the tumour growth time was observed following the treatment of thermotherapy (TT) only group (2.5 days), radiation therapy only group (4.5 days), and the combined radio-thermotherapy group (10 days). Immunohistochemical staining revealed a reduced hypoxia region with vascular disruption and extensive tumour necrosis following the combined radio-thermotherapy. These results indicate that GdIONP-mediated hyperthermia can improve the efficacy of RT by its dual functions in high temperature (temperature greater than 45 °C)-mediated thermal ablation and mild-temperature hyperthermia (MTH) (temperature between 39 and 42 °C)-mediated reoxygenation.

Preclinical evaluation of an MR-compatible microwave ablation system and comparison with a standard microwave ablation system in an ex vivo bovine liver model.

OBJECTIVE: Evaluation of a newly developed MR-compatible microwave ablation system with focus on ablation performance and comparison with a corresponding standard microwave ablation system. MATERIALS AND METHODS: A total of 52 ablations were performed with a non-cooled microwave ablation system in an ex vivo bovine liver model using the following settings: [A] 16G-standard antenna, 2 cm active tip, 2.4 m cable; [B] MR-compatible 16G-antenna, 2 cm active tip, 2.4 m cable; [C] MR-compatible 16G-antenna, 2 cm active tip, extended 6 m cable; and [D] MR-compatible 16G-antenna, 4 cm active tip, extended 6 m cable. Ablation durations were 3, 5 and 10 min, and additionally 15 min for [D]. Ablations zones were measured for short-axis diameter (SA) and long-axis diameter (LA). Settings [A]-[C] were compared regarding SA, volume (V) and generator energy output (E) with analysis of variance and Tukey-Kramer post hoc test. Ablation performance of the MR-compatible settings [C] and [D] were compared regarding SA, V, E and sphericity index (SA/LA) with unpaired t-test. p < 0.05 was considered as statistically significant. RESULTS: No significant differences were found between [A], [B] and [C] regarding SA and V (10 min; SA[A] = 25.8 ± 2.4 mm, SA[B] = 25.3 ± 1.9 mm, SA[C] = 25.0 ± 2.0 mm, p = 0.88; V[A] = 17.8 ± 4.4 cm³, V[B] = 16.6 ± 3.0 cm³, V[C] = 17.8 ± 2.7 cm³, p = 0.85); however, the highest energy output was measured for setting [C] (10 min; [A]: 9.9 ± 0.5 kJ, [B]: 10.1 ± 0.5 kJ, [C]: 13.1 ± 0.3 kJ, p < 0.001). SA, V and E were significantly larger with setting [D] than [C] with 10 min ablations (SA[C] = 25.0 ± 2.0 mm, SA[D] = 34.0 ± 2.9 mm, p = 0.003; V[C] = 17.8 ± 2.7 cm³, V[D] = 39.4 ± 7.5 cm³, p = 0.007; E[C] = 13.1 ± 0.3 kJ, E[D] = 16.7 ± 0.8 kJ, p = 0.002) without significant difference in sphericity index (SA/LA[C] = 0.46 ± 0.02, SA/LA[D] = 0.52 ± 0.04, p = 0.08). CONCLUSION: The tested MR-compatible system can be used without loss of ablation performance compared to the standard system.

MiR-34-a acts as a suppressor in neuroblastoma progression by targeting CD44.

OBJECTIVE: To verify whether micro ribonucleic acid 34-a can exert its negative effects in human neuroblastoma cells. METHODS: The study was conducted at The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China during 15 months (from March 2015 to about June 2016). Quantitative reverse transcription polymerase chain reaction was used to find the differences of micro ribonucleic acid 34-a between metastatic neuroblastoma and primary tumours. We transfected micro ribonucleic acid 34-a mimics and antisense oligonucleotides into neuroblastoma cell line to explore its function in vitro through the variations. Additionally, fluorescent reporter assay was used to clear the targeting site of micro ribonucleic acid 34-a and CD44. Furthermore, protein levels of CD44, the putative target gene of micro ribonucleic acid 34-a, was assessed after transfection by Western blot. RESULTS: Compared to the primary neuroblastoma tumours, micro ribonucleic acid 34-a was lower in metastatic neuroblastoma using quantitative reverse transcription polymerase chain reaction (p<0.05). Transfection of micro ribonucleic acid 34-a mimics and antisense oligonucleotides into a neuroblastoma cell line significantly affected cellular activity, migration and invasion (p<0.05_. Fluorescent reporter assays proved that CD44 acts as the target spot of micro ribonucleic acid 34-a for repression in post-transcription level. Micro ribonucleic acid 34-a inhibited the expression of CD44, and increased concentration of micro ribonucleic acid 34-a mimics resulted in a greater decrease in the expression of CD44. CONCLUSIONS: Micro ribonucleic acid 34-a might suppress the progression of neuroblastoma through inhibiting the expression of the potential target gene CD44.

Advances in IL-7 Research on Tumour Therapy.

Interleukin-7 (IL-7) is a versatile cytokine that plays a crucial role in regulating the immune system's homeostasis. It is involved in the development, proliferation, and differentiation of B and T cells, as well as being essential for the differentiation and survival of naïve T cells and the production and maintenance of memory T cells. Given its potent biological functions, IL-7 is considered to have the potential to be widely used in the field of anti-tumour immunotherapy. Notably, IL-7 can improve the tumour microenvironment by promoting the development of Th17 cells, which can in turn promote the recruitment of effector T cells and NK cells. In addition, IL-7 can also down-regulate the expression of tumour growth factor-ß and inhibit immunosuppression to promote anti-tumour efficacy, suggesting potential clinical applications for anti-tumour immunotherapy. This review aims to discuss the origin of IL-7 and its receptor IL-7R, its anti-tumour mechanism, and the recent advances in the application of IL-7 in tumour therapy.

Photothermal and ferroptosis synergistic therapy for liver cancer using iron-doped polydopamine nanozymes.

An innovative nanozyme, iron-doped polydopamine (Fe-PDA), which integrates iron ions into a PDA matrix, conferred peroxidase-mimetic activity and achieved a substantial photothermal conversion efficiency of 43.5 %. Fe-PDA mediated the catalysis of H2O2 to produce toxic hydroxyl radicals (•OH), thereby facilitating lipid peroxidation in tumour cells and inducing ferroptosis. Downregulation of solute carrier family 7 no. 11 (SLC7A11) and solute carrier family 3 no. 2 (SLC3A2) in System Xc- resulted in decreased intracellular glutathione (GSH) production and inactivation of the nuclear factor erythroid 2-related factor 2 (NRF2)-glutathione peroxidase 4 (GPX4) pathway, contributing to ferroptosis. Moreover, the application of photothermal therapy (PTT) enhanced the effectiveness of chemodynamic therapy (CDT), accelerating the Fenton reaction for targeted tumour eradication while sparing adjacent non-cancerous tissues. In vivo experiments revealed that Fe-PDA significantly hampered tumour progression in mice, emphasizing the potential of the dual-modality treatment combining CDT and PTT for future clinical oncology applications.

Membrane-coated nanoparticles as a biomimetic targeted delivery system for tumour therapy.

Drug therapy towards tumours often causes adverse effects because of their non-specific nature. Membrane-coated technology and membrane-coated nanoparticles provide an advanced and promising platform of targeted and safe delivery. By camouflaging the nanoparticles with natural derived or artificially modified cell membranes, the nano-payloads are bestowed with properties from cell membranes such as longer circulation, tumour or inflammation-targeting, immune stimulation, augmenting the performance of traditional therapeutics. In this review, we review the development of membrane coating technology, and summarise the technical details, physicochemical properties, and research status of membrane-coated nanoparticles from different sources in tumour treatment. Finally, we also look forward to the prospects and challenges of transforming membrane coating technology from experiment into clinical use. Taken together, membrane-coated nanoparticles are bound to become one of the most potential anti-tumour strategies in the future.

Characterisation of the cell and molecular biological effect of peptide-based daunorubicin conjugates developed for targeting pancreatic adenocarcinoma (PANC-1) cell line.

Pancreatic adenocarcinoma is one of the tumours with the worst prognosis, with a 5-year survival rate of 5-10%. Our aim was to find and optimise peptide-based drug conjugates with daunorubicin (Dau) as the cytotoxic antitumour agent. When conjugated with targeting peptides, the side effect profile and pharmacokinetics of Dau can be improved. The targeting peptide sequences (e.g. GSSEQLYL) we studied were originally selected by phage display. By Ala-scan technique, we identified that position 6 in the parental sequence (Dau=Aoa-LRRY-GSSEQLYL-NH2, ConjA) could be modified without the loss of antitumour activity (Dau=Aoa-LRRY-GSSEQAYL-NH2, Conj03: 14. 9% viability). Our results showed that the incorporation of p-chloro-phenylalanine (Dau=Aoa-LRRY-GSSEQF(pCl)YL-NH2, Conj16) further increased the antitumour potency (10-5 M: 9.7% viability) on pancreatic adenocarcinoma cells (PANC-1). We found that conjugates containing modified GSSEQLYL sequences could be internalised to PANC-1 cells and induce cellular senescence in the short term and subsequent apoptotic cell death. Furthermore, the cardiotoxic effect of Dau was markedly reduced in the form of peptide conjugates. In conclusion, Conj16 had the most effective antitumor activity on PANC-1 cells, which makes this conjugate promising for developing new targeted therapies without cardiotoxic effects.

B-cell performance in chemotherapy: Unravelling the mystery of B-cell therapeutic potential.

BACKGROUND AND MAIN BODY: The anti-tumour and tumour-promoting roles of B cells in the tumour microenvironment (TME) have gained considerable attention in recent years. As essential orchestrators of humoral immunity, B cells potentially play a crucial role in anti-tumour therapies. Chemotherapy, a mainstay in cancer treatment, influences the proliferation and function of diverse B-cell subsets and their crosstalk with the TME. Modulating B-cell function by targeting B cells or their associated cells may enhance chemotherapy efficacy, presenting a promising avenue for future targeted therapy investigations. CONCLUSION: This review explores the intricate interplay between chemotherapy and B cells, underscoring the pivotal role of B cells in chemotherapy treatment. We summarise promising B-cell-related therapeutic targets, illustrating the immense potential of B cells in anti-tumour therapy. Our work lays a theoretical foundation for harnessing B cells in chemotherapy and combination strategies for cancer treatment. KEY POINTS: Chemotherapy can inhibit B-cell proliferation and alter subset distributions and functions, including factor secretion, receptor signalling, and costimulation. Chemotherapy can modulate complex B-cell-T-cell interactions with variable effects on anti-tumour immunity. Targeting B-cell surface markers or signalling improves chemotherapy responses, blocks immune evasion and inhibits tumour growth. Critical knowledge gaps remain regarding B-cell interactions in TME, B-cell chemoresistance mechanisms, TLS biology, heterogeneity, spatial distributions, chemotherapy drug selection and B-cell targets that future studies should address.

In vitro and in vivo evaluation of Bombesin-MMAE conjugates for targeted tumour therapy.

Targeted tumour therapy has proved to be an efficient alternative to overcome the limitations of conventional chemotherapy. The upregulation of the bombesin receptor 2 (BB2) in several malignancies and the advantages offered by peptide drug conjugates over antibody drug conjugates in terms of production and tumour targeting motivated us to synthesise and test bombesin conjugates armed with the tubulin binder monomethyl auristatin E. The widely used Val-Cit-PABC was initially included as cathepsin cleavable self-immolative linker for the release of the free drug. However, the poor stability of the Val-Cit-conjugates in mouse plasma encouraged us to consider the optimised alternatives Glu-Val-Cit-PABC and Glu-Gly-Cit-PABC. Conjugate BN-EVcM1, featuring Glu-Val-Cit-PABC, combined suitable stability (t(½) in mouse and human plasma: 8.4 h and 4.6 h, respectively), antiproliferative activity in vitro (IC50 = 29.6 nM on the human prostate cancer cell line PC-3) and the full release of the free payload within 24 h. Three conjugates, namely BN-EGcM1, BN-EVcM1 and BN-EVcM2, improved the accumulation of MMAE in PC-3 human prostate cancer xenograft mice models, compared to the administration of the free drug. Among them, BN-EVcM1 also stood out for the significantly extended survival of mice in in vivo acute efficacy studies and for the significant inhibition of the growth of a PC-3 tumour in mice in both acute and chronic efficacy studies.

The Emerging Role of Cell Membrane-coated Nanomaterials in Cancer Therapy.

This review investigates the revolutionary application of cell membrane-coated nanoparticles (CMNPs) as a promising avenue for cancer therapy within the embryonic landscape of nanotechnology. Nanoparticles, pivotal in cancer treatment, are systematically examined for their diverse physicochemical structures, categorized as organic (lipid-based, protein-based, and polymer-assisted) and inorganic (carbon-based and metal) varieties. A significant focus is placed on CMNPs, which serve as an innovative drug delivery vehicle, overcoming limitations associated with conventional nanoparticle therapies. This manuscript accurately explores the advantages and challenges of various cell membranes, including those derived from cancer cells, red blood cells, platelets, stem cells, and white blood cells. Importance is placed on their roles in enhancing drug delivery precision, immune system circumvention, and targeted recognition. Detailed insights into the crafting of CMNPs are provided, elucidating membrane extraction and fusion techniques, such as sonication, extrusion, co-extrusion, and microfluidic electroporation. Maintaining membrane integrity during extraction and the benefits of coating techniques in augmenting biocompatibility and targeted drug delivery are underscored. This comprehensive resource consolidates the latest advancements in targeted drug delivery, positioning itself at the forefront of nanotechnology and biomedicine research. Encapsulating various methodologies like membrane extrusion, electrospray, and chemical conjugation, this manuscript showcases the expanding toolbox available to researchers in this dynamic field. Focusing on the unique characteristics of CMNPs, this review explores their multifaceted applications in biomedical research, particularly in tumour therapy. It provides an indepth analysis of the biocompatibility of CMNPs, their stability, immune evasion capabilities, targeted drug delivery precision, increased payload capacity, and retained biological functionality. The manuscript outlines current applications and future prospects of CMNPs in targeted chemotherapy, photothermal and photodynamic therapy, immunotherapy, gene therapy, and innovative therapeutic methods. It concludes by highlighting the advantages of CMNPs in tumour therapy and their transformative potential in reshaping the landscape of cancer treatment.

Efficient drug-delivery using magnetic nanoparticles--biodistribution and therapeutic effects in tumour bearing rabbits.

To treat tumours efficiently and spare normal tissues, targeted drug delivery is a promising alternative to conventional, systemic administered chemotherapy. Drug-carrying magnetic nanoparticles can be concentrated in tumours by external magnetic fields, preventing the nanomaterial from being cleared by metabolic burden before reaching the tumour. Therefore in Magnetic Drug Targeting (MDT) the favoured mode of application is believed to be intra-arterial. Here, we show that a simple yet versatile magnetic carrier-system (hydrodynamic particles diameter <200nm) accumulates the chemotherapeutic drug mitoxantrone efficiently in tumours. With MDT we observed the following drug accumulations relative to the recovery from all investigated tissues: tumour region: 57.2%, liver: 14.4%, kidneys: 15.2%. Systemic intra-venous application revealed different results: tumour region: 0.7%, liver: 14.4 % and kidneys: 77.8%. The therapeutic outcome was demonstrated by complete tumour remissions and a survival probability of 26.7% (P=0.0075). These results are confirming former pilot experiments and implying a milestone towards clinical studies. FROM THE CLINICAL EDITOR: This team of investigators studied drug carrying nanoparticles for magnetic drug targeting (MDT), demonstrating the importance of intra-arterial administration resulting in improved clinical outcomes in the studied animal model compared with intra-venous.

Advancement in transporter-oriented nanoplatforms for cancer therapy.

Except for cell-surface receptors, a range of transporters have been exploited as targets for the delivery of novel anti-tumour nanomaterials. Transporters, which are essential for delivering nutrients for the biosynthesis of mammalian cells, are significantly expressed in a range of tumour types; their expression is mostly tissue- and site-specific. The unique functional and expression characteristics of transporters make them ideal targets for mediating the selective delivery of nanomaterials to cancer cells, thus promoting cell accumulation, and enhancing the penetration of nanomaterials into biological barriers before they can specifically target cancer cells. In this review, we discuss the unique function of cancer-related transporters in the initiation and development of tumours, as well as the use of transporter-targeted nanocarriers in tumour-targeting therapy. First, the expression of various transporters in tumorigenesis and development is reviewed; this is followed by a discussion of the latest advances in targeted drug delivery strategies based on transporter nanocarriers. Finally, we review the molecular mechanisms and targeting efficiency of transporter-mediated nanocarriers. This review provides a state-of-the-art synthesis of this discipline and will facilitate the generation of new concepts for the design of highly efficacious and tumour-targeting nanocarriers.

Progress in the study of FOXO3a interacting with microRNA to regulate tumourigenesis development.

FOXO3a is a protein of the forkhead box family that inhibits tumour cell growth. One of the regulatory modes affecting the role of FOXO3a is microRNA targeting and degradation of its mRNA expression, and conversely, aberrant expression of FOXO3a as a transcription factor also influences microRNA levels. We summarized the results of the regulatory interactions of twenty-five microRNAs with FOXO3a in five types of malignant tumours and found that dual microRNAs synergize with FOXO3a to inhibit breast cancer cell growth including two groups; Three individual microRNAs collaborated with FOXO3a to restrain hepatocellular carcinoma progression; Twelve individual microRNAs antagonized FOXO3a to promote the development of a single tumour cell, respectively; and five microRNAs antagonized FOXO3a to contribute to the progression of more than two types of tumours. The above findings demonstrated the tumour suppressor effect of FOXO3a, but another result revealed that miR-485-5p and miR-498 inhibited the growth of hepatocellular carcinoma cells by antagonizing FOXO3a when acting in combination with other long-stranded non-coding RNAs, respectively, suggesting that FOXO3a at this moment plays the function of promoting the tumour progression. The PI3K/AKT, Snail, VEGF-NRP1, and Wnt/ß-catenin signalling pathways perform crucial roles in the above process. It is anticipated that the above studies will assist in understanding the effects of FOXO3a-MicroRNA interactions in cancer genesis and development, and provide new perspectives in the treatment of malignant tumours.