Biological Therapy Of Cancer Research Articles

Progress of Mesoporous Silica Coated Gold Nanorods for Biological Imaging and Cancer Therapy.

For unique surface plasmon absorption and fluorescence characteristics, gold nanorods have been developed and widely employed in the biomedical field. However, limitations still exist due their low specific surface area, instability and tendency agglomerate in cytoplasm. Mesoporous silica materials have been broadly applied in field of catalysts, adsorbents, nanoreactors, and drug carriers due to its unique mesoporous structure, highly comparative surface area, good stability and biocompatibility. Therefore, coating gold nanorods with a dendritic mesopore channels can effectively prevent particle agglomeration, while increasing the specific surface area and drug loading efficiency. This review discusses the advancements of GNR@MSN in synthetic process, bio-imaging technique and tumor therapy. Additionally, the further application of GNR@MSN in imaging-guided treatment modalities is explored, while its promising superior application prospect is highlighted. Finally, the issues related to in vivo studies are critically examined for facilitating the transition of this promising nanoplatform into clinical trials.

Oncolytic Viruses, An Emerging Anti-Cancer Immunotherapy: Current Achievements and Future Directions

Oncolytic viruses (OVs) are currently influencing biological cancer therapy. It is a recently created immunotherapy that has been approved to treat cancer and can promote the death of specific cell types to promote antitumor immunological effects. Given the complicated conditions in the tumor micro environment (TME), trials involving the use of OVs demonstrated that OVs could potentially be utilized independently or in combination with other therapies like radiotherapy, chemotherapy, immune checkpoint inhibitors, as well as surgery. While immune suppression against tumors is of critical importance in OV therapy, concurrent antiviral immune responses should also be taken into consideration. Because of this, antiviral immune responses limit OV infections and replication, which also restricts the oncolytic effects of OVs. Recent studies on the operation and mechanics of OVs and how they are employed in clinics has produced results that are encouraging for the future. This review outlined the traits and biological categories of potential OVs, presented the findings of clinical trials, and discussed combinations with other forms of cancer therapy.

Deep immunophenotyping reveals clinically distinct cellular states and ecosystems in large-scale colorectal cancer

Determining the diverse cell types in the tumor microenvironment (TME) and their organization into cellular communities, is critical for understanding the biological heterogeneity and therapy of cancer. Here, we deeply immunophenotype the colorectal cancer (CRC) by integrative analysis of large-scale bulk and single cell transcriptome of 2350 patients and 53,137 cells. A rich landscape of 42 cellular states and 7 ecosystems in TMEs is uncovered and extend the previous immune classifications of CRC. Functional pathways and potential transcriptional regulators analysis of cellular states and ecosystems reveal cancer hallmark-related pathways and several critical transcription factors in CRC. High-resolution characterization of the TMEs, we discover the potential utility of cellular states (i.e., Monocytes/Macrophages and CD8 T cell) and ecosystems for prognosis and clinical therapy selection of CRC. Together, our results expand our understanding of cellular organization in TMEs of CRC, with potential implications for the development of biomarkers and precision therapies.

Conjugated Polymeric Materials in Biological Imaging and Cancer Therapy.

Conjugated polymers (CPs) have attracted much attention in the fields of chemistry, medicine, life science, and material science. Researchers have carried out a series of innovative researches and have made significant research progress regarding the unique photochemical and photophysical properties of CPs, expanding the application range of polymers. CPs are polymers formed by the conjugation of multiple repeating light-emitting units. Through precise control of their structure, functional molecules with different properties can be obtained. Fluorescence probes with different absorption and emission wavelengths can be obtained by changing the main chain structure. By modifying the side chain structure with water-soluble groups or selective recognition molecules, electrostatic interaction or specific binding with specific targets can be achieved; subsequently, the purpose of selective recognition can be achieved. This article reviews the research work of CPs in cell imaging, tumor diagnosis, and treatment in recent years, summarizes the latest progress in the application of CPs in imaging, tumor diagnosis, and treatment, and discusses the future development direction of CPs in cell imaging, tumor diagnosis, and treatment.

Ocular surface complications following biological therapy for cancer.

Novel and highly effective biological agents developed to treat cancer over the past two decades have also been linked to multiple adverse outcomes, including unanticipated consequences for the cornea. This review provides an overview of adverse corneal complications of biological agents currently in use for the treatment of cancer. Epidermal growth factor receptor inhibitors and immune checkpoint inhibitors are the two classes of biological agents most frequently associated with corneal adverse events. Dry eye, Stevens-Johnson syndrome, and corneal transplant rejection have all been reported following the use of immune checkpoint inhibitors. The management of these adverse events requires close collaboration between ophthalmologists, dermatologists, and oncologists. This review focuses in depth on the epidemiology, pathophysiology, and management of ocular surface complications of biological therapies against cancer.

A Curcumin‐Based MOF Embedded Ag NPs and Modified with Polydopamine for Dual‐Drug Delivery and Dual Biological Window Responsive Synergetic Cancer Therapy

AbstractA dual‐drug delivery, pH‐responsive composite nanoplatform (MAPD NPs) that can respond to two biological windows is developed to improve the efficacy of synergetic chemotherapic/photothermal/chemodynamic therapy (CDT) against tumors. This nanoplatform is surface‐modified polydopamine (PDA) with excellent biocompatibility as the shell and Ag NPs as the catalyst for CDT. The curcumin (Cur) acts as an organic ligand to be encapsulated in metal−biomolecule frameworks (Bio‐MOFs) by self‐assembly, and Bio‐MOF acts as a delivery carrier to deliver of DOX•HCl and then releases the Cur when it degrades in vivo. Moreover, Bio‐MOF can be taken up by cells faster and accelerate cell death compared to free Cur. PDA modification enables MAP (PDA@MOF‐Ag) to have photothermal properties under 808 and 1064 nm light irradiation, which not only improves the biocompatibility of MAP but also makes it produce high heat and abundant ·OH. The photothermal performance of MAP is stable after irradiation at 808 or 1064 nm, and the photothermal conversion efficiency reaches 63.57% and 26.25%. The survival rate of HeLa cells co‐incubation with MAPD NPs after irradiation at 808 and 1064 nm decreases to 19.52 ± 0.69% and 30.48 ± 0.49%, respectively, providing a feasible scheme for the realization of deep tumor killing.

Identification of Signature Genes in the PD-1 Relative Gastric Cancer Using a Combined Analysis of Gene Expression and Methylation Data.

The morbidity and mortality rates for gastric cancer (GC) rank second among all cancers, indicating the serious threat it poses to human health, as well as human life. This study aims to identify the pathways and genes as well as investigate the molecular mechanisms of tumor-related genes in gastric cancer (GC). We compared differentially expressed genes (DEGs) and differentially methylated genes (DMGs) in gastric cancer and normal tissue samples using The Cancer Genome Atlas (TCGA) data. The Kyoto Encyclopedia of Gene and Genome (KEGG) and the Gene Ontology (GO) enrichment analysis' pathway annotations were conducted on DMGs and DEGs using a clusterProfiler R package to identify the important functions, as well as the biological processes and pathways involved. The intersection of the two was chosen and defined as differentially methylated and expressed genes (DMEGs). For DMEGs, we used the principal component analysis (PCA) to differentiate gastric cancer from adjacent samples. The linear discriminant analysis method was applied to categorize the samples using DMEGs methylation data and DMEGs expression profiles data and was validated using the leave-one-out cross-validation (LOOCV) method. We plotted the ROC curve for the classification and calculated the AUC (area under the ROC curve) value for a more intuitive view of the classification effect. We also used the NetworkAnalyst 3.0 tool to analyze DMEGs, using DrugBank to acquire information on protein-drug interactions and generate a network map of gene-drug interactions. We identified a total of 971 DMGs in 188 PD-1 negative and 187 PD-1 positive gastric cancer samples obtained from TCGA. The KEGG and GO enrichment analysis showed the involvement of the regulation of ion transmembrane transport, collagen-containing extracellular matrix, cell-cell junction, and peptidase regulator activity. We simultaneously obtained 1,189 DEGs, out of which 986 were downregulated, while 203 were upregulated in tumors. The enriched analysis of the GO's and KEGG's pathways indicated that the most significant pathways included an intestinal immune network for IgA production, Staphylococcus aureus infection, cytokine-cytokine receptor interaction, and viral protein interaction with cytokine and cytokine receptor, which have previously been linked with gastric cancer. The compound DB01830 can bind well to the active site of the LCK protein and shows good stability, thus making it a potential inhibitor of the LCK protein. To observe the relationship between DMEGs' expression and prognosis, we observed 10 genes, among which were TRIM29, TSPAN8, EOMES, PPP1R16B, SELL, PCED1B, IYD, JPH1, CEACAM5, and RP11-44K6.2. Their high expressions were related to high risks. Besides, those genes were validated in different internal and external validation sets. These results may provide potential molecular biological therapy for PD-1 negative gastric cancer.

Facile preparation of poly(N-isopropylacrylamide)/graphene oxide nanocomposites for chemo-photothermal therapy

ABSTRACT Carbon-based nanomaterials, such as carbon nanotubes, fullerenes, nanodiamonds, and graphene, have been investigated for various biomedical applications, including biological imaging, photothermal therapy, drug/gene delivery, cancer therapy, biosensors, and electrochemical sensors. Graphene oxide (GO) has unique physicochemical properties and can be used to restore conductivity through oxidation. In this study, we developed poly(N-isopropylacrylamide) (PNIPAM)-based nanogel systems containing GO for controlled in vitro drug delivery. The photothermal effects of the PNIPAM/GO- and PNIPAMAAM/GO-based nanogel systems were enhanced. The release of DOX from the PNIPAM/GO-based nanogel was achieved using the photothermal effect of near-infrared irradiation. Using a Cell Counting Kit-8 assay, the cytotoxicity of all conditions demonstrated that the PNIPAM composite-based nanogels were biocompatible with no significance.

“Nano Killers” Activation by permonosulfate enables efficient anaerobic microorganisms disinfection

The development of effective nanomaterials for killing anaerobic bacteria is essential for human health and economic development. Here, we propose a new bactericidal mechanism where theoretical calculations are in good agreement with experimental results. The “poison arrow-head” of MoS2 nanosheets enables the vigorous extraction of lipids from the cell membrane. Based on density functional calculations, oxidation active species (OAS) are generated due to the strong adsorption energy between S vacancies in MoS2 and chemical substrates (permonosulfate (PMS) and H2O). These OAS can be visualized as numerous moving “nano killers”, constantly oxidizing the lipids around MoS2; thereby, re-releasing the surface of the sharp knife. The process of physical extraction collaborated with chemical oxidation not only precisely positions the cell membrane but also allows for continuous sterilization. This work digs into the mechanism of anaerobic bacterial sterilization, which sheds significant light on biological analysis, antibacterial, cancer therapy, and anti microbiologically influenced corrosion.

Avidin-Biotin functionalized self-assembled protein nanoparticles as EGFR targeted therapeutics for the treatment of lung cancer: characterization and cell viability

Gefitinib targeting efficiency can be modified via enhancing its hydrophobicity and poor bioavailability by conjugating it with biotin-streptavidin conjugated Bovine serum albumin nanoparticles as a hotspot in the field of biological therapy for human cancer. The study aims to develop and characterize lyophilized Biotin-Streptavidin conjugated Bovine serum albumin nanoparticles containing Gefitinib prepared by desolvation method. As protein being the most amendable to surface functionalization were prepared by conjugating them with strongest interaction, that is, Biotin-Streptavidin. The Desolvation method is based on nanoprecipitation method that reduces the solubility of drug and polymer in aqueous solution by using desolvating agents in order to prepare protein nanoparticles that were further functionalized by biotinylation followed with streptavidin conjugation for enhancement in affinity and specificity. Protein NPs were found to be monodisperse with particle size in range of 130 ± 5.131 and 174 ± 3.055 with the approximate negatively surface charge zeta potential of −9 mv. The drug loading and the entrapment efficiency was found to be 16% and 74 ± 2.64% with 8 days of sustained drug release at the physiological pH. Cytotoxicity studies after 72 h shown better cell growth inhibition with biotinylated streptavidin conjugated bovine serum albumin nanoparticles containing gefitinib with reduced side effect and more apoptosis of cells as compared to gefitinib loaded bovine serum albumin nanoparticles and free gefitinib.

Streamlining breast cancer and colorectal cancer biosimilar regulations to improve treatment access in Latin America: an expert panel perspective.

In a multiday conference, a panel of Latin American experts in biological cancer therapies and health economics were provided with questions to address the barriers restricting access to biosimilars in Latin America, specifically for patients with breast cancer and colorectal cancer, for whom biosimilars can be a path forward to increasing access to care. During the conference, responses were discussed and edited until a consensus was achieved. The regulatory challenges identified in the conference included heterogenous regulations, non-adherence to regulatory pathways, scarcity of market opportunity, inadequate naming of biosimilars by only using international non-proprietary names, imprecise use of interchangeability and substitution, and insufficient traceability and pharmacovigilance. Recommendations were developed to improve the implementation of regulatory pathways and reliable procurement strategies that increase access to these therapies with adequate traceability and outcome measures; efforts from all involved stakeholders will be crucial. These recommendations can serve as a strategy for biosimilar adoption in other countries in a similar situation.

A Multifunctional Vanadium-Iron-Oxide Nanoparticle Eradicates Hepatocellular Carcinoma via Targeting Tumor and Endothelial Cells.

Nanoparticles are widely used in biological research and cancer therapy. In hepatocellular carcinoma, several nanoplatforms have been synthesized and studied to improve the drug efficacy; however, these nanoplatforms are still insufficient to eradicate tumors. Herein, we have synthesized a novel vanadium (V)-iron-oxide (ION) nanoparticle (VIO) that combines chemodynamic, photothermal, and diagnostic capacities to enhance the tumor suppression effect in one agent with multiple functions. In the in vitro models, hepatocellular carcinoma cells are significantly inhibited by VIO-based nanoagents. The mechanistic study validates that VIO increases reactive oxygen species (ROS), which led to apoptosis and ferroptosis resulting in cell death. To our surprise, VIO targets not only tumor cells but also endothelial cells. In addition to inducing cell death, VIO also blocks tube formation and cell migration in human umbilical vein endothelial cell (HUVEC) and C166 models, indicating an antiangiogenic potential. In mouse tumor models, VIO retards tumor growth and induces apoptosis in tumor tissues. Furthermore, a significant blood vessel regression is seen in VIO-treated groups accompanied with larger necrotic areas. More interestingly, the activation of photothermal therapy completely eradicates tumor tissues. Taken together, this VIO nanoplatform could be a powerful anticancer candidate for nanodrug development.

Cancer, General Principles of Biological Treatments

Biological therapy for cancer is a type of treatment that uses the body's immune system to kill cancer cells. Biological therapy for cancer is used in the treatment of many types of cancer to prevent or slow tumor growth and to prevent the spread of cancer. Biological therapy for cancer often causes fewer toxic side effects than do other cancer treatments. The goal of biological therapy for cancer is to induce your immune system to recognize and kill cancer cells. Your body's immune system fights invaders, such as germs, throughout your body. Your immune system should also recognize cancer cells as abnormal, but it doesn't always do that. Cancer cells can develop an ability to hide from immune system cells. Or cancer cells can disable or inhibit immune system cells from acting [1,2]. In general, biological therapies work by: 1. Inducing the immune system to attack cancer cells. There are several ways biological therapy treatments can achieve this goal. As an example, chemicals that stimulate your immune system cells could be injected into your body. Or a sample of your immune system cells could be trained in a lab to attack cancer cells before being reintroduced to your body. 2. Making cancer cells easier for your immune system to recognize. Biological therapy can also target the cancer cells, turning on or off cell signals that help them elude the immune system cells. As an example, drugs called immune checkpoint inhibitors can target specific chemical receptors on cancer cells, blocking the signals the cancer cells send to suppress the immune system.

Surface-Functionalized NdVO4:Gd3+ Nanoplates as Active Agents for Near-Infrared-Light-Triggered and Multimodal-Imaging-Guided Photothermal Therapy.

Development of nanotheranostic agents with near-infrared (NIR) absorption offers an effective tool for fighting malignant diseases. Lanthanide ion neodymium (Nd3+)-based nanomaterials, due to the maximum absorption at around 800 nm and unique optical properties, have caught great attention as potential agents for simultaneous cancer diagnosis and therapy. Herein, we employed an active nanoplatform based on gadolinium-ion-doped NdVO4 nanoplates (NdVO4:Gd3+ NPs) for multiple-imaging-assisted photothermal therapy. These NPs exhibited enhanced NIR absorption and excellent biocompatibility after being grafted with polydopamine (pDA) and bovine serum albumin (BSA) layers on their surface. Upon expose to an 808 nm laser, these resulting NPs were able to trigger hyperthermia rapidly and cause photo-destruction of cancer cells. In a xenograft tumor model, tumor growth was also significantly inhibited by these photothermal agents under NIR laser irradiation. Owing to the multicomponent nanostructures, we demonstrated these nanoagents as being novel contrast agents for in vivo magnetic resonance (MR) imaging, X-ray computed tomography (CT), photoacoustic (PA) imaging, and second biological window fluorescent imaging of tumor models. Thus, we believe that this new kind of nanotherapeutic will benefit the development of emerging nanosystems for biological imaging and cancer therapy.

Oncolytic viral vectors in the era of diversified cancer therapy: from preclinical to clinical.

With the in-depth research and wide application of immunotherapy recently, new therapies based on oncolytic viruses are expected to create new prospects for cancer treatment via eliminating the suppression of the immune system by tumors. Currently, an increasing number of viruses are developed and engineered, and various virus vectors based on effectively stimulating human immune system to kill tumor cells have been approved for clinical treatment. Although the virus can retard the proliferation of tumor cells, the choice of oncolytic viruses in biological cancer therapy is equally critical given their therapeutic efficacy, safety and adverse effects. Moreover, previously known oncolytic viruses have not been systematically classified. Therefore, in this review, we summarized and distinguished the characteristics of several common types of oncolytic viruses: herpes simplex virus, adenovirus, measles virus, Newcastle disease virus, reovirus and respiratory syncytial virus. Subsequently, we outlined that these oncolytic viral vectors have been transformed from preclinical studies in combination with immunotherapy, radiotherapy, chemotherapy, and nanoparticles into clinical therapeutic strategies for various advanced solid malignancies or circulatory system cancers.

MO527: The Active Ingredient in the Nuphar Lutea Plant, 6,6′: Dihydroxythiobinupharidine (DTBN) Ameliorates Kidney Fibrosis, Inflammation and Anemia in a Mouse Model of Chronic Kidney Disease (CKD)

Abstract BACKGROUND AND AIMS EPO resistance and iron deficiency in CKD-related anemia are associated with an increase in inflammatory cytokines associated with the innate immune response, such as IL-6, IL-1 and TNF-α. Recently (Bandach et al. Sci Reports 2021) we reported that kidney fibrosis and anemia of CKD can be worsened or relieved when IL1 effects are enhanced or inhibited respectively. The Water lily (Nuphar lutea) plant has been widely used as a traditional remedy for the treatment of rheumatism, scars, pain and more. Gopas, Golan-Goldhirsh et al. (Cancer Biology Therapy 2009) extracted an active ingredient from the family of nupharidines: 6,6′-Dihydroxythiobinupharidine (DTBN), which showed anti-inflammatory properties, mainly through the inhibition of NF-κB. The purpose of this study was to test the effects of DTBN in a mouse model of CKD-associated anemia. METHOD 8 weeks old male C57BL/6 mice were divided into three groups: control, CKD (induced by adenine diet) and CKD-DTBN. CKD groups were injected with saline-DMSO or 30 µg DTBN, every 2 days and sacrificed after 3 weeks from dietary intervention. RESULTS Serum urea and kidney TGFβ mRNA were significantly decreased in CKD- DTBN versus CKD. Kidney histology in CKD mice showed macrophage infiltration and renal fibrosis, which was ameliorated in CKD-DTBN. A significant improvement in inflammation indices (blood lymphocytes, kidney and liver IL-6 and p-STAT3, liver CRP), as well as kidney immunoreactive NF-κB and F4\80, which were increased in CKD, were decreased in CKD-DTBN. CKD anemia indices (hemoglobin, hematocrit and red blood cell (RBC) count) significantly improved in CKD-DTBN. Kidney HIF-2α and EPO mRNA were significantly decreased in both uremic groups, but was unchanged in CKD- DTBN versus CKD. However, serum iron and transferrin saturation significantly increased in CKD-DTBN versus CKD. CONCLUSION Uremic mice treated with DTBN show improvement in kidney fibrosis, inflammation and anemia indices. Thus, DTBN may be a novel therapeutic alternative for CKD and its complications.

Biologics and Dentistry: Implications for Dental Treatment and Patient Management

This article discusses the implications of biologics on dental treatment and patient management. There is limited information available on the dental relevance of biologics, and, with increasing numbers of patients undertaking biological therapy for autoimmune diseases, cancer, and osteoporosis among other conditions, comprehensive research is needed. Information gathered from clinical trials and literature reviews was used to consolidate information for general dental practitioners (GDPs). CPD/Clinical Relevance: To update GDPs on biologics, highlight the importance of taking a thorough medical history and encourage discussion on management of patients taking biologics in general dental practice.

Tumor Suppression via Visually Derailing Intracellular Sialylation With Multifunctional Nanoparticles

Sialylation plays important roles in tumor-related physiological process. Therefore, intervention of sialylation has great potential to explore new paths for tumor therapy. In view of the immune modulation of sialic acid (SA) on tumor, this work designs a multifunctional mesoporous silica nanoparticle (MFMSN) to derail intracellular sialylation for tumor suppression. The galactose groups covered on MFMSN act as sialylation substrates to bind intracellular SAs competitively, which inhibits the SA expression on tumor cell surface. The derailed intracellular sialylation can be visualized on living cells and in vivo by specifically binding the sialylated galactose with phenylboronic acid labeled ssDNA probe released from the pore of MFMSN to induce DNA strand displacement, which recovers the fluorescence of dsDNA probe covered on MFMSN surface. The derailment of sialylation efficiently suppresses tumor growth on mice, demonstrating the great potentials of the designed strategy for revealing SA-related biological processes and clinical cancer therapy.

Fluorescent gold nanoclusters stabilized on halloysite nanotubes: in vitro study on cytotoxicity

Fluorescent gold nanoclusters (AuNCs) with an average diameter of 2.7 ± 1.0 nm stabilized with 11-mercaptoundecanoic acid were supported on halloysite nanotubes modified with aminosilane. The cytotoxicity of the obtained fluorescent material was investigated in A549 human cells. The AuNCs stabilized on halloysite showed good uptake by the cells. The material did not cause a pronounced toxic effect and visible membrane damage within the 25–50 μg/mL concentration range. An increase in nanocomposite concentration to 100 μg/mL led to massive cell death via apoptosis. This concentration-dependent toxicity mechanism allows for using AuNCs stabilized on halloysite for halloysite visualization in biological objects, bioimaging, and cancer therapy.

Perspectives on Oncolytic Salmonella in Cancer Immunotherapy-A Promising Strategy.

Since the first reported spontaneous regression of tumors in patients with streptococcus infection, cancer biological therapy was born and it evolved into today’s immunotherapy over the last century. Although the original strategy was unable to impart maximal therapeutic benefit at the beginning, it laid the foundations for the development of immune checkpoint blockade and CAR-T which are currently used for cancer treatment in the clinics. However, clinical applications have shown that current cancer immunotherapy can cause a series of adverse reactions and are captious for patients with preexisting autoimmune disorders. Salmonellae was first reported to exert antitumor effect in 1935. Until now, numerous studies have proved its potency as an antitumor agent in the near future. In this review, we summarize the currently available data on the antitumor effects of Salmonella, and discussed a possibility of integrating Salmonella into cancer immunotherapy to overcome current obstacles.