Hyaluronic Acid Stabilized Doxorubicin Nano-Precipitations for Osteosarcoma Treatment

2022 ◽  
Vol 12 (3) ◽  
pp. 500-505
Mouzhang Huang ◽  
Limei Zeng ◽  
Rongping Zhu ◽  
Gongqun Chen ◽  
Haijian Wu ◽  

Doxorubicin (Dox) is a wide-spectrum drug to treat different kinds of cancers. However, in clinical practice, Dox usually showed untargeted distributions to the other organs, which can cause serious side effects, such as cardiotoxity. Herein, the formulation of Dox into nanoparticles is critical to enhance its distribution to tumors. Herein, we used polysaccharide, hyaluronic acid, to stabilize the Dox to form nano-precipitations (PD NPs) for the therapy of osteosarcoma. The PD NPs showed enhanced drug accumulation to tumor cells and realized better anticancer effects than free drugs.

1987 ◽  
Vol 26 (05) ◽  
pp. 202-205 ◽  
J. Fass ◽  
S. Truong ◽  
U. Büll ◽  
V. Schumpelick ◽  
R. Bares

Radioimmunoscintigraphy (RIS) with 111ln- and 131 I-labelled monoclonal anti bodies (MAbs) against CEA and/or CA 19-9 was performed in 83 patients with various gastrointestinal carcinomas. A total of 276 body regions could be examined. The results of planar scintigraphy and SPECT were compared intraindividually. Using 111 In-labelled MAbs the sensitivity of RIS was significantly improved by SPECT (88.9 vs. 52.4% with planar scintigraphy, p <0.01). For131 l-labelled MAbs the effect was smaller (83.9 vs. 65.6% with planar scintigraphy, n.s.). This finding can be explained by different kinetics and biodistribution of the used MAb preparations.111 In-labelled MAbs with long whole-body retention and rapid blood clearance reveal ideal qualities for SPECT; on the other hand, the short whole-body retention of131 l-labelled MAbs leads to small count rates and therefore long counting times that make delayed SPECT unsuitable in clinical practice

2020 ◽  
Vol 27 (13) ◽  
pp. 2118-2132 ◽  
Aysegul Hanikoglu ◽  
Hakan Ozben ◽  
Ferhat Hanikoglu ◽  
Tomris Ozben

: Elevated Reactive Oxygen Species (ROS) generated by the conventional cancer therapies and the endogenous production of ROS have been observed in various types of cancers. In contrast to the harmful effects of oxidative stress in different pathologies other than cancer, ROS can speed anti-tumorigenic signaling and cause apoptosis of tumor cells via oxidative stress as demonstrated in several studies. The primary actions of antioxidants in cells are to provide a redox balance between reduction-oxidation reactions. Antioxidants in tumor cells can scavenge excess ROS, causing resistance to ROS induced apoptosis. Various chemotherapeutic drugs, in their clinical use, have evoked drug resistance and serious side effects. Consequently, drugs having single-targets are not able to provide an effective cancer therapy. Recently, developed hybrid anticancer drugs promise great therapeutic advantages due to their capacity to overcome the limitations encountered with conventional chemotherapeutic agents. Hybrid compounds have advantages in comparison to the single cancer drugs which have usually low solubility, adverse side effects, and drug resistance. This review addresses two important treatments strategies in cancer therapy: oxidative stress induced apoptosis and hybrid anticancer drugs.

2020 ◽  
Vol 27 (28) ◽  
pp. 4720-4740 ◽  
Ting Yang ◽  
Xin Sui ◽  
Bing Yu ◽  
Youqing Shen ◽  
Hailin Cong

Multi-target drugs have gained considerable attention in the last decade owing to their advantages in the treatment of complex diseases and health conditions linked to drug resistance. Single-target drugs, although highly selective, may not necessarily have better efficacy or fewer side effects. Therefore, more attention is being paid to developing drugs that work on multiple targets at the same time, but developing such drugs is a huge challenge for medicinal chemists. Each target must have sufficient activity and have sufficiently characterized pharmacokinetic parameters. Multi-target drugs, which have long been known and effectively used in clinical practice, are briefly discussed in the present article. In addition, in this review, we will discuss the possible applications of multi-target ligands to guide the repositioning of prospective drugs.

2019 ◽  
Vol 14 (3) ◽  
pp. 280-291 ◽  
Jaleh Varshosaz ◽  
Farshid Hassanzadeh ◽  
Batool Hashemi-Beni ◽  
Mohsen Minaiyan ◽  
Saeedeh Enteshari

Background: Due to the low water solubility of Docetaxel (DTX), it is formulated with ethanol and Tween 80 with lots of side effects. For this reason, special attention has been paid to formulate it in new drug nano-carriers. Objective: The goal of this study was to evaluate the safety, antitumor activity and tissue distribution of the novel synthesized Raloxifene (RA) targeted polymeric micelles. Methods: DTX-loaded RA-targeted polymeric micelles composed of poly(styrene-maleic acid)- poly(amide-ether-ester-imide)-poly(ethylene glycol) (SMA-PAEE-PEG) were prepared and their antitumor activity was studied in MC4-L2 tumor-bearing mice compared with non-targeted micelles and free DTX. Safety of the micelles was studied by Hematoxylin and Eosin (H&E) staining of tumors and major organs of the mice. The drug accumulation in the tumor and major organs was measured by HPLC method. Results: The results showed better tumor growth inhibition and increased survival of mice treated with DTX-loaded in targeted micelles compared to the non-targeted micelles and free DTX. Histopathological studies, H&E staining of tumors and immunohistochemical examination showed the potential of DTX-loaded RA-targeted micelles to inhibit tumor cells proliferation. The higher accumulation of the DTX in the tumor tissue after injection of the micelles compared to the free DTX may indicate the higher uptake of the targeted micelles by the G-Protein-Coupled Estrogen Receptors (GPER). Conclusion: The results indicate that RA-conjugated polymeric micelles may be a strong and effective drug delivery system for DTX therapy and uptake of the drug into tumor cells, and overcome the disadvantages and side effects of conventional DTX.

Allergy ◽  
2014 ◽  
Vol 69 (3) ◽  
pp. 372-379 ◽  
J. M. Foster ◽  
S. Schokker ◽  
R. Sanderman ◽  
D. S. Postma ◽  
T. van der Molen

2021 ◽  
Vol 4 (1) ◽  
Giovanni S. Offeddu ◽  
Cynthia Hajal ◽  
Colleen R. Foley ◽  
Zhengpeng Wan ◽  
Lina Ibrahim ◽  

AbstractThe glycocalyx on tumor cells has been recently identified as an important driver for cancer progression, possibly providing critical opportunities for treatment. Metastasis, in particular, is often the limiting step in the survival to cancer, yet our understanding of how tumor cells escape the vascular system to initiate metastatic sites remains limited. Using an in vitro model of the human microvasculature, we assess here the importance of the tumor and vascular glycocalyces during tumor cell extravasation. Through selective manipulation of individual components of the glycocalyx, we reveal a mechanism whereby tumor cells prepare an adhesive vascular niche by depositing components of the glycocalyx along the endothelium. Accumulated hyaluronic acid shed by tumor cells subsequently mediates adhesion to the endothelium via the glycoprotein CD44. Trans-endothelial migration and invasion into the stroma occurs through binding of the isoform CD44v to components of the sub-endothelial extra-cellular matrix. Targeting of the hyaluronic acid-CD44 glycocalyx complex results in significant reduction in the extravasation of tumor cells. These studies provide evidence of tumor cells repurposing the glycocalyx to promote adhesive interactions leading to cancer progression. Such glycocalyx-mediated mechanisms may be therapeutically targeted to hinder metastasis and improve patient survival.

2020 ◽  
Vol 11 (1) ◽  
Pierre Auloge ◽  
Julien Garnon ◽  
Joey Marie Robinson ◽  
Sarah Dbouk ◽  
Jean Sibilia ◽  

Abstract Objectives To assess awareness and knowledge of Interventional Radiology (IR) in a large population of medical students in 2019. Methods An anonymous survey was distributed electronically to 9546 medical students from first to sixth year at three European medical schools. The survey contained 14 questions, including two general questions on diagnostic radiology (DR) and artificial intelligence (AI), and 11 on IR. Responses were analyzed for all students and compared between preclinical (PCs) (first to third year) and clinical phase (Cs) (fourth to sixth year) of medical school. Of 9546 students, 1459 students (15.3%) answered the survey. Results On DR questions, 34.8% answered that AI is a threat for radiologists (PCs: 246/725 (33.9%); Cs: 248/734 (36%)) and 91.1% thought that radiology has a future (PCs: 668/725 (92.1%); Cs: 657/734 (89.5%)). On IR questions, 80.8% (1179/1459) students had already heard of IR; 75.7% (1104/1459) stated that their knowledge of IR wasn’t as good as the other specialties and 80% would like more lectures on IR. Finally, 24.2% (353/1459) indicated an interest in a career in IR with a majority of women in preclinical phase, but this trend reverses in clinical phase. Conclusions Development of new technology supporting advances in artificial intelligence will likely continue to change the landscape of radiology; however, medical students remain confident in the need for specialty-trained human physicians in the future of radiology as a clinical practice. A large majority of medical students would like more information about IR in their medical curriculum; almost a quarter of students would be interested in a career in IR.

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 181
Francesca Zonta ◽  
Christian Borgo ◽  
Camila Paz Quezada Meza ◽  
Ionica Masgras ◽  
Andrea Rasola ◽  

CK2 is a Ser/Thr protein kinase overexpressed in many cancers. It is usually present in cells as a tetrameric enzyme, composed of two catalytic (α or α’) and two regulatory (β) subunits, but it is active also in its monomeric form, and the specific role of the different isoforms is largely unknown. CK2 phosphorylates several substrates related to the uncontrolled proliferation, motility, and survival of cancer cells. As a consequence, tumor cells are addicted to CK2, relying on its activity more than healthy cells for their life, and exploiting it for developing multiple oncological hallmarks. However, little is known about CK2 contribution to the metabolic rewiring of cancer cells. With this study we aimed at shedding some light on it, especially focusing on the CK2 role in the glycolytic onco-phenotype. By analyzing neuroblastoma and osteosarcoma cell lines depleted of either one (α) or the other (α’) CK2 catalytic subunit, we also aimed at disclosing possible pro-tumor functions which are specific of a CK2 isoform. Our results suggest that both CK2 α and α’ contribute to cell proliferation, survival and tumorigenicity. The analyzed metabolic features disclosed a role of CK2 in tumor metabolism, and suggest prominent functions for CK2 α isoform. Results were also confirmed by CK2 pharmacological inhibition. Overall, our study provides new information on the mechanism of cancer cells addiction to CK2 and on its isoform-specific functions, with fundamental implications for improving future therapeutic strategies based on CK2 targeting.

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