scholarly journals AFP-Inhibiting Fragments for Drug Delivery: The Promise and Challenges of Targeting Therapeutics to Cancers

2021 ◽  
Vol 9 ◽  
Author(s):  
Bo Lin ◽  
Xu Dong ◽  
Qiujiao Wang ◽  
Wei Li ◽  
Mingyue Zhu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Delivery ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Immune Cells ◽  
Targeted Chemotherapy ◽  
Patients With Cancer ◽  
Important Target ◽  
Intracellular Proteins ◽  
New Strategy

Alpha fetoprotein (AFP) plays a key role in stimulating the growth, metastasis and drug resistance of hepatocellular carcinoma (HCC). AFP is an important target molecule in the treatment of HCC. The application of AFP-derived peptides, AFP fragments and recombinant AFP (AFP-inhibiting fragments, AIFs) to inhibit the binding of AFP to intracellular proteins or its receptors is the basis of a new strategy for the treatment of HCC and other cancers. In addition, AIFs can be combined with drugs and delivery agents to target treatments to cancer. AIFs conjugated to anticancer drugs not only destroy cancer cells with these drugs but also activate immune cells to kill cancer cells. Furthermore, AIF delivery of drugs relieves immunosuppression and enhances chemotherapy effects. The synergism of immunotherapy and targeted chemotherapy is expected to play an important role in enhancing the treatment effect of patients with cancer. AIF delivery of drugs will be an available strategy for the targeted treatment of cancer in the future.

scholarly journals Multifaceted Functions of Platelets in Cancer: From Tumorigenesis to Liquid Biopsy Tool and Drug Delivery System

2020 ◽  
Vol 21 (24) ◽  
pp. 9585
Author(s):  
Melania Dovizio ◽  
Patrizia Ballerini ◽  
Rosa Fullone ◽  
Stefania Tacconelli ◽  
Annalisa Contursi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Cells ◽  
Immune Cells ◽  
Expression Patterns ◽  
Cell Communication ◽  
Antiplatelet Agents ◽  
Cell Types ◽  
Disease Monitoring ◽  
Crucial Component ◽  
Numerous Cell

Platelets contribute to several types of cancer through plenty of mechanisms. Upon activation, platelets release many molecules, including growth and angiogenic factors, lipids, and extracellular vesicles, and activate numerous cell types, including vascular and immune cells, fibroblasts, and cancer cells. Hence, platelets are a crucial component of cell–cell communication. In particular, their interaction with cancer cells can enhance their malignancy and facilitate the invasion and colonization of distant organs. These findings suggest the use of antiplatelet agents to restrain cancer development and progression. Another peculiarity of platelets is their capability to uptake proteins and transcripts from the circulation. Thus, cancer-patient platelets show specific proteomic and transcriptomic expression patterns, a phenomenon called tumor-educated platelets (TEP). The transcriptomic/proteomic profile of platelets can provide information for the early detection of cancer and disease monitoring. Platelet ability to interact with tumor cells and transfer their molecular cargo has been exploited to design platelet-mediated drug delivery systems to enhance the efficacy and reduce toxicity often associated with traditional chemotherapy. Platelets are extraordinary cells with many functions whose exploitation will improve cancer diagnosis and treatment.

scholarly journals EpCAM- and/or NCAM-Expressing Hepatocellular Carcinoma in Which Behavior of Hepatic Progenitor Cell Marker-Positive Cells Are Followed

2019 ◽  
Vol 13 (1) ◽  
pp. 118-124 ◽  
Author(s):  
Atsunori Tsuchiya ◽  
Takeshi Suda ◽  
Chiyumi Oda ◽  
Atsushi Kimura ◽  
Kazunori Hosaka ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Cells ◽  
Vascular Invasion ◽  
Progenitor Cell ◽  
Cell Marker ◽  
Hepatic Progenitor Cell ◽  
Invasion And Metastasis ◽  
Metastatic Lesions ◽  
Important Target ◽  
Hepatocellular Carcinomas

Hepatic progenitor cell (HPC) marker-positive hepatocellular carcinomas (HCCs) have recently been extensively analyzed, and their prognosis has been reported as poor compared to HPC marker-negative HCCs. However, previous studies have analyzed the existence of HPC marker-positive cancer cells only in primary lesions, as well as the recurrence rate and prognosis of such tumors. Here, we are the first to report the behavior of HPC marker-positive cancer cells during vascular invasion and metastasis of an HCC. We concurrently analyzed EpCAM- and/or NCAM-expressing cancer cells in the primary, vascular invasion, and metastatic lesions of an HCC. An HCC which includes EpCAM- and/or NCAM-expressing cancer cells has not been previously reported. EpCAM- and/or NCAM-positive cancer cells invaded the vessels and formed heterogeneous populations of these HPC marker-positive cancer cells with HPC marker-negative cancer cells. The frequency of HPC marker-positive cancer colonies and cells in vessels was higher than that in the primary HCC. In the metastatic lesions, EpCAM-positive cancer cells were more frequently detected than NCAM-positive cancer cells, indicating that EpCAM may be more important than NCAM for cancer cell settlement in the metastatic lesions. Furthermore, bigger metastatic tumors tended to include HPC marker-positive cancer cells, suggesting that HPC marker-positive cancer cells have a growth advantage in the metastatic lesions. These results showed that HPC marker-positive cancer cells would be important for vascular invasion and metastasis and suggested that HPC marker-positive cancer cells are an important target in HCC treatment.

scholarly journals A new combination strategy to enhance apoptosis in cancer cells by using nanoparticles as biocompatible drug delivery carriers

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ertan Kucuksayan ◽  
Fatih Bozkurt ◽  
Mustafa Tahsin Yilmaz ◽  
Aslinur Sircan-Kucuksayan ◽  
Aysegul Hanikoglu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Clinical Studies ◽  
Encapsulation Efficiency ◽  
In Vitro Release ◽  
New Combination ◽  
Combination Strategy ◽  
Normal Cells

AbstractSome experimental and clinical studies have been conducted for the usage of chemotherapeutic drugs encapsulated into nanoparticles (NPs). However, no study has been conducted so far on the co-encapsulation of doxorubicin (Dox) and epoxomicin (Epo) into NPs as biocompatible drug delivery carriers. Therefore, we investigated if co-encapsulation of doxorubicin (Dox) and/or epoxomicin (Epo) into NPs enhance their anticancer efficiency and prevent drug resistance and toxicity to normal cells. We synthesized Dox and/or Epo loaded poly (lactic-co-glycolic acid) (PLGA) NPs using a multiple emulsion solvent evaporation technique and characterized them in terms of their particle size and stability, surface, molecular, thermal, encapsulation efficiency and in vitro release properties. We studied the effects of drug encapsulated NPs on cellular accumulation, intracellular drug levels, oxidative stress status, cellular viability, drug resistance, 20S proteasome activity, cytosolic Nuclear Factor Kappa B (NF-κB-p65), and apoptosis in breast cancer and normal cells. Our results proved that the nanoparticles we synthesized were thermally stable possessing higher encapsulation efficiency and particle stability. Thermal, morphological and molecular analyses demonstrated the presence of Dox and/or Epo within NPs, indicating that they were successfully loaded. Cell line assays proved that Dox and Epo loaded NPs were less cytotoxic to single-layer normal HUVECs than free Dox and Epo, suggesting that the NPs would be biocompatible drug delivery carriers. The apoptotic index of free Dox and Epo increased 50% through their encapsulation into NPs, proving combination strategy to enhance apoptosis in breast cancer cells. Our results demonstrated that the co-encapsulation of Dox and Epo within NPs would be a promising treatment strategy to overcome multidrug resistance and toxicity to normal tissues that can be studied in further in vivo and clinical studies in breast cancer.

scholarly journals Application of mesoporous silica nanoparticles for drug delivery to cancer cells

2020 ◽  
pp. 5-15
Keyword(s):  
Drug Delivery ◽  
Drug Resistance ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Cancer Cells ◽  
Efflux Pump ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Loading ◽  
Controlled Drug Release ◽  
Multi Drug Resistance

Cancer is one of the main causes of death worldwide. Chemotherapy is the most common method for cancer therapy which represent non-specific side effects on normal cells and tissues and drug resistance in cancer cells. There are two main mechanisms for Multi Drug Resistance (MDR) in cancer cells including: drug efflux pump and activation of anti-apoptotic pathways. Cancer chemotherapy disadvantages can be overcome by using nanoparticulate drug delivery systems like Mesoporous Silica Nanoparticles (MSNs) that have been used as drug delivery system since 2001. The present review included synthesis, targeted (active or passive) drug delivery to cancer cells, co-delivery of anticancer drugs and siRNA by MSNs and its toxicity. This review revealed that MSNs are good candidate for drug delivery to cancer cells due to its unique properties including: controllable pore and particle sizes, thermal and chemical stability, modifications of outer and inner surfaces of nanoparticles for drug and siRNA loading, attachment of ligand for targeted drug delivery, high drug loading capacity and controlled drug release, biocompatibility and biodegradation in aqueous medium.

PTX encapsulated by an XG–DOX conjugate for combination therapy against multi-drug resistance

RSC Advances ◽  
2016 ◽  
Vol 6 (109) ◽  
pp. 107606-107612 ◽  
Author(s):  
Zhuli Huang ◽  
Xuan Xie ◽  
Jean Felix Mukerabigwi ◽  
Chang Wang ◽  
Shufang Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Resistance ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Drug Delivery System ◽  
Delivery System ◽  
Multi Drug Resistance ◽  
New Type ◽  
Dual Drug

A new type of targeted dual drug delivery system was designed and possesses outstanding advantages over ordinary systems, proving effective against MDR cancer cells.

Drug delivery by a self-assembled DNA tetrahedron for overcoming drug resistance in breast cancer cells

2013 ◽  
Vol 49 (20) ◽  
pp. 2010 ◽  
Author(s):  
Kyoung-Ran Kim ◽  
Da-Rae Kim ◽  
Taemin Lee ◽  
Ji Young Yhee ◽  
Byeong-Su Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Dna Tetrahedron ◽  
Self Assembled

Freezing-Assisted Intracellular Drug Delivery to Multi-Drug Resistant Cancer Cells

2008 ◽  
Author(s):  
Ka Yaw Teo ◽  
Bumsoo Han
Keyword(s):  
Drug Delivery ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Plasma Membranes ◽  
Clinical Effectiveness ◽  
Multi Drug Resistance ◽  
Drug Resistant ◽  
Intracellular Drug Delivery ◽  
Protein Transporters

The efficacy of chemotherapy is significantly impaired by multi-drug resistance (MDR) of cancer cells. The mechanism of MDR is associated with the overexpression of certain ATP-binding cassette protein transporters in plasma membranes. These transporters actively keep intracellular drug concentration below the cell-killing threshold by extruding cytotoxic drugs. Various strategies to overcome MDR have been proposed and have shown promising results at the laboratory level. However, pharmacokinetic alteration of co-administered anticancer agents reduces their clinical effectiveness. This leads to increased toxicity and undesirable side effects at effective concentrations [1]. Hence, a clinically feasible strategy to overcome the phenomenon of MDR is highly desired.

scholarly journals Quantitative evaluation of cellular internalization of polymeric nanoparticles within laryngeal cancer cells and immune cells for enhanced drug delivery

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Li-Juan Ma ◽  
Ruichao Niu ◽  
Xi Wu ◽  
Jun Wu ◽  
En Zhou ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Cells ◽  
Immune Cells ◽  
Laryngeal Carcinoma ◽  
Polymeric Nanoparticles ◽  
Giant Cells ◽  
Carcinoma Cells ◽  
Cellular Internalization ◽  
Tumor Drug Delivery ◽  
Quantitative Fluorescence

AbstractClinical translation of poly (lactic-co-glycolic acid) (PLGA)-based nanomedicine is limited, partly because of the poor delivery efficiency resulting from non-specific phagocytosis by phagocytes. Understanding the nanoparticle interplay between cancer cells and immune cells remains largely elusive. In this study, a quantitative investigation on cellular internalization of fluorescent PLGA particles (100 nm, 500 nm, and 1 µm) against laryngeal carcinoma cells with or without monocytes/macrophages in monoculture or co-culture systems was first performed. PLGA particles at concentrations of 5–20 µg/mL show superior biocompatibility except for 500 nm and 1 µm PLGA particles at 20 µg/mL slightly reduce cell viability. Microscopic observation has discovered all three sizes of particles are effectively ingested by both cancer cells and macrophages; however, quantitative fluorescence examination has disclosed that the uptake index of cancer cells (mean intracellular particle fluorescence per cancer cell normalized to that of per macrophage) is substantially declined for all PLGA particles in co-cultures compared to that in monocultures (1.35–1.05, 1.50–0.59, and 1.4–0.47 for 100 nm, 500 nm, and 1 µm particles, respectively). Quantitative analysis using flow cytometry further confirmed the reduced uptake index of cancer cells in co-cultures, but higher particle counts per macrophage. It has also been found that the formation of multinucleated giant cells via the fusion of macrophages increased after PLGA treatment, which could be further exploited as a potential approach for tumor drug delivery. Overall, these findings provide new insights into the interaction of nanoparticle-immune-cancer cells, which may facilitate the application of PLGA-based nanocarriers for the treatment of laryngeal carcinoma.

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