Archive for the ‘Popular Advances’ Category

April 2023 Popular Advances Articles

Welcome to April’s Popular Advances article round up!

Every month we update our 2023 RSC Advances Popular Advances Article Collection to showcase all of the articles selected by our reviewers and handling editors as Popular Advances in 2023. Don’t forget to come back next month to check out our latest Popular articles.

We hope you enjoy reading and as always, all of our articles are open access so you can easily share your favourites online and with your colleagues.

Explore the full collection!

Novel asymmetrical azines appending 1,3,4-thiadiazole sulfonamide: synthesis, molecular structure analyses, in silico ADME, and cytotoxic effect
Samir Bondock, Tallah Albarqi, Ibrahim A. Shaaban and Moaz M. Abdou
RSC Adv., 2023, 13, 10353-10366

A molybdenum disulfide/nickel ferrite-modified voltammetric sensing platform for ultra-sensitive determination of clenbuterol under the presence of an external magnetic field
Van Manh Tien, Van Hoang Ong, Tuyet Nhung Pham, Nguyen Quang Hoa, Thi Lan Nguyen, Pham Duc Thang, Le Khanh Vinh, Pham Thi Nhat Trinh, Doan Thi Ngoc Thanh, Le Minh Tung and Anh-Tuan Le
RSC Adv., 2023, 13, 10577-10591

Potential role of a novel biphenanthrene derivative isolated from Aerides falcata in central nervous system diseases
Bachtiar Rivai, Hasriadi, Peththa Wadu Dasuni Wasana, Chaisak Chansriniyom, Pasarapa Towiwat, Yanyong Punpreuk, Kittisak Likhitwitayawuid, Pornchai Rojsitthisak and Boonchoo Sritularak
RSC Adv., 2023,13, 10757-10767

Analysis and process evaluation of metal dopant (Zr, Cr)-promoted Ga-modified ZSM-5 for the oxidative dehydrogenation of propane in the presence and absence of CO2
Abbas Jawad and Sura Ahmed
RSC Adv., 2023, 13, 11081-11095

Valorization of homogeneous linear catechyl lignin: opportunities and challenges
Yibing Li, Xianzhi Meng, Rongqian Meng, Ting Cai, Yunqiao Pu, Zhi-Min Zhao and Arthur J. Ragauskas
RSC Adv., 2023, 13, 12750-12759

Salazinic acid attenuates male sexual dysfunction and testicular oxidative damage in streptozotocin-induced diabetic albino rats
Kishore Naidu Killari, Haritha Polimati, D. S. N. B. K. Prasanth, Gagandeep Singh, Siva Prasad Panda, Girija Sastry Vedula and Vinay Bharadwaj Tatipamula
RSC Adv., 2023, 13, 12991-13005

 

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RSC Popular Advances Interview with Hossein Eshghi

We are very pleased to introduce Professor Hossein Eshghi,  who is the corresponding author on the paper, Immobilized Cu(0) nanoparticles on montmorillonite-modified with benzalkonium chloride (MMT-BAC@Cu(0)): as an eco-friendly and proficient heterogeneous nano-catalyst for green synthesis of 5-substituted 1H-tetrazoles.  The manuscript was well received by reviewers and was handpicked by our reviewers and handling editors to be part of our Popular Advances collection.

Professor Hossein Eshghi told us more about his research group and the work that went into this study and what he hopes to achieve in the future. You can explore other articles in our 2023 Popular Advances online collection here!

The authors: 

Dr. Eshghi,
Ferdowsi University of Mashhad, Iran

Dr. Rounaghi,
Birjand University of Technology, Iran

F. Pirani,
Ferdowsi University of Mashhad, Iran

  1. Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?

This paper introduces an eco-friendly and efficient approach for the synthesize of 5-substituted 1H-tetrazole derivatives from raw materials of benzonitrile and sodium azide through the [2+3] cycloaddition reaction as well as 2-(1H-tetrazole-5-yl) acrylonitrile derivatives as the preferred product from raw materials of aldehyde, malononitrile, and sodium azide through multicomponent domino reactions (MDRs) in the presence of the MMT-BAC@Cu(0) nanoclay as a proficient heterogeneous catalysis in mild conditions.

  1. How big an impact could your results potentially have?

The MMT-BAC@Cu(0) nanocatalyst used benefits from properties such as high surface reactivity, biocompatibility, non-toxicity, and inexpensiveness. Some advantages of the green solvent used in the study are non-flammability, high solubility, degradability, inexpensiveness, recyclability, and non-volatility. This method was proven to be more efficient than previous methods, which employed hazardous organic solvents and toxic metals and performed the process with a longer reaction time. Using the proposed approach, the reaction was made in a shorter time under green conditions with good to excellent efficiency and without the need for additional reagents.

  1. Could you explain the motivation behind this study?

In this study, Cu(0) nanoparticles supported on organo-modified montmorillonite with benzalkonium chloride (MMT-BAC@Cu(0)) were synthesized and used as a heterogeneous and green catalyst for synthesis of 5-substituted 1H-tetrazoles. A recent focus has come to using clay minerals as heterogeneous and green catalysts. In this regard, montmorillonite (MMT) clay has drawn particular attention due to its high abundance, cation exchange capacity, and other high surface areas. It is no wonder that the synthesis of tetrazoles has turned into a hot topic in the organic field so dramatically that it has drawn huge focus and attention in academic research and industrial areas. However, because that the protocols used in the synthesis of 5-substituted 1H-tetrazoles usually include the application of common organic solvents or catalysts whose synthesis path is not green and economical. We sought to change the protocol for the synthesis of 5-substituted 1H-tetrazoles through the design of stable nanoclay as catalysts with interesting features such as the stability of synthesized nanocatalysts, non-leaching with products, and widespread application in the synthesis of two significant classes of 5-substituted 1H-tetrazoles through the [2+3] cycloaddition reaction and multicomponent domino reactions (MDRs) reactions. Moreover, while observing the principles of green chemistry, which is one of the important issues in green chemistry and chemical engineering, we utilized the novel green nano catalyst and solvent (DESs).

  1. In your opinion, what are the key design considerations for your study?

The current project aims to develop a biocompatible nanocatalyst based on immobilized Cu(0) nanoparticles on montmorillonite -modified with benzalkonium chloride (MMT-BAC@Cu(0)) for the synthesis of 5-substituted-1H-tetrazoles under mild and green conditions. The advantages of availability, low cost, non-toxicity, and biocompatibility of clay were our focus in synthesizing this nanoclay catalyst in this project. The method’s advantages include good to excellent product yields, mild conditions, easy work-up, short reaction times and easy reuse of the nano catalyst.

  1. Which part of the work towards this paper proved to be most challenging?

Since the clay is a naturally formed mineral, its composition, properties and even the organic chemical modifiers used during subsequent modification process can alter in different ways. Hence, the selection of a proper nanoclay material is of crucial importance. The MMT-BAC@Cu(0) nanocatalyst used benefits from properties such as high surface reactivity, biocompatibility, non-toxicity, and inexpensiveness. Some advantages of the green solvent used in the study are non-flammability, high solubility, degradability, expensiveness, recyclability, and non-volatility. This method was proven to be more efficient than previous methods, which employed hazardous organic solvents and toxic metals and performed the process with a longer reaction time.

  1. What aspect of your work are you most excited about at the moment?

An eco-friendly and efficient approach for the synthesize of 2-(1H-tetrazole-5-yl) acrylonitrile derivatives as the preferred product from raw materials through multicomponent domino reactions (MDRs) was introduced. This is significant because heterocyclic compounds are of great pharmacological importance and changes in the conditions of the synthesis protocol to achieve sustainable development are among the important issues we considered in this paper.

7.What is the next step? What work is planned?

We hope that the presented method can be generalized in the future to synthesize heterocyclic derivatives with important biological properties to be used in valuable research projects by adhering to the principles of green chemistry. This work opens us a window for the synthesis of other chemical derivatives using heterogenous clay based nanocatalysis.

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RSC Advances Popular Advances Interview with Dr Machhindra K. Lande

We are very pleased to introduce Dr. Machhindra K. Lande who is the corresponding author of the RSC Advances article, Silica supported lanthanum trifluoroacetate and trichloroacetate as an efficient and reusable water compatible Lewis acid catalyst for synthesis of 2,4,5-triarylimidazoles via a solvent-free green approach. This was well received by reviewers and was handpicked by our handling editors to be part of our Popular Advances collection – a big congratulations to all the authors!

Dr Lande told us more about his research group and the work that went into this study and what he hopes to achieve in the future. You can explore other articles in our 2023 Popular Advances online collection here!

Meet the Author

Dr. M. K. Lande is a professor and head of the department of chemistry at Dr. B. A. M. University, Aurangabad (Maharashtra, India). His research group includes Mr. Dnyaneshwar Purushottam Gholap, Mr. Ramdas Huse and Mr. Dipake Sudarshan, who were actively involved in contributing towards this popular advances article. Dr. M. K. Lande’s group’s research area includes Natural and synthetic zeolites catalysts, Lewis acid catalysts for organic transformation, mixed metal oxides as catalysts for organic transformations, metal-organic frameworks and DFT studies of chemical compounds using Gaussian 09 software.

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?

The present research work is mainly focused on the development of novel water-compatible, environment-friendly and economically cheaper heterogeneous Lewis acid catalysts as competitive alternatives to highly expensive Metal triflate catalysts.

How big an impact could your results potentially have?

The currently prepared water-competent Lewis acid catalyst shows excellent catalytic efficiency in 2,4,5-triaryl imidazole synthesis via green route, compared to many catalysts, especially Metal triflate Lewis acid catalyst. Further, these Lewis catalysts were prepared by commercially available cheaper starting material hence it is economically more favourable as compared to highly expensive Metal triflate Lewis acid.

Could you explain the motivation behind this study?

By considering the special attention and importance of Lewis acid as a catalyst in many industrial processes and organic transformations, we had planned to design novel water-compatible Lewis acid. However, currently, many conventional Lewis acids and green Lewis acids were used in the reaction, but they have many limitations.
Among all these, metal triflate is one of the most widely used green Lewis acids but they are highly expensive and moisture sensitive. In regard to this, we have developed economically favourable and environment-friendly green silica supported Lanthanum trifluoroacetate and trichloroacetate Lewis acid catalysts.

In your opinion, what are the key design considerations for your study?

The key design considerations of the present research work are as follows

– Water-competent Green Lewis acid catalysts
– Highly efficient, clean, environment-friendly and recyclable Lewis acids
– Catalyst work superiorly in water and organic solvents
– Solvent-free green synthesis in a short time with excellent product yield

Which part of the work towards this paper proved to be most challenging?

The synthesis of present Lewis acids was found to be most challenging as special precaution and care were needed during the handling of trifluoracetic acid and trichloroacetic acid.

What aspect of your work are you most excited about at the moment?

The present Lewis acid can become a good competitive alternative to green Lewis acid catalysts, especially highly expensive metal triflate Lewis acids.


What is the next step? What work is planned?

To design and develop more novel, environment-friendly and economically favorable green Lewis acid catalysts & utilize them in various industrially demanded processes and organic transformations.

 

Silica supported lanthanum trifluoroacetate and trichloroacetate as an efficient and reusable water compatible Lewis acid catalyst for synthesis of 2,4,5-triarylimidazoles via a solvent-free green approach

Dnyaneshwar Purushottam Gholap,

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February 2023 Popular Advances Articles

Welcome to February’s Popular Advances article round up!

Every month we update our 2023 RSC Advances Popular Advances Article Collection to showcase all of the articles selected by our reviewers and handling editors as Popular Advances in 2023. Don’t forget to come back next month to check out our latest Popular articles.

We hope you enjoy reading and as always, all of our articles are open access so you can easily share your favourites online and with your colleagues.

Explore the full collection!

 

In vitro anti-inflammatory, in silico molecular docking and molecular dynamics simulation of oleanane-type triterpenes from aerial parts of Mussaenda recurvata
Mai Dinh Tri, Nguyen Tan Phat, Phan Nhat Minh, Mai Thanh Chi, Bui Xuan Hao, Tran Nguyen Minh An, Mahboob Alam, Nguyen Van Kieu, Van-Son Dang, Tran Thi Ngoc Mai and Thuc-Huy Duong
RSC Adv., 2023, 13, 5324-5336

Aqueous phase hydrogenolysis of glycerol with in situ generated hydrogen over Ni/Al3Fe1 catalyst: effect of the calcination temperature
Raquel Raso, Alejandro Lete, Lucía García, Joaquín Ruiz, Miriam Oliva and Jesús Arauzo
RSC Adv., 2023, 13, 5483-5495

Immobilized Cu(0) nanoparticles on montmorillonite-modified with benzalkonium chloride (MMT-BAC@Cu(0)): as an eco-friendly and proficient heterogeneous nano-catalyst for green synthesis of 5-substituted 1H-tetrazoles
Fatemeh Pirani, Hossein Eshghi and S. Amin Rounaghi
RSC Adv., 2023, 13, 6160-6170

Million-atom molecular dynamics simulations reveal the interfacial interactions and assembly of plant PSII-LHCII supercomplex
Ruichao Mao, Han Zhang, Lihua Bie, Lu-Ning Liu and Jun Gao
RSC Adv., 2023, 13, 6699-6712

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January 2023 Popular Advances Articles

Welcome to January’s Popular Advances article round up!

Every month we update our 2023 RSC Advances Popular Advances Article Collection to showcase all of the articles selected by our reviewers and handling editors as Popular Advances in 2023. Don’t forget to come back next month to check out our latest Popular articles.

We hope you enjoy reading and as always, all of our articles are open access so you can easily share your favourites online and with your colleagues.

Explore the full collection!

 

High-efficiency and durable V–Ti–Nb ternary catalyst prepared by a wet-solid mechanochemical method for sustainably producing acrylic acid via acetic acid–formaldehyde condensation
Jun Liu, Youjun Yan, Meng Lian, Jimei Song, Yongqi Yang, Guofu Huang, Miao Wang, Xinzhen Feng and Weijie Ji
RSC Adv., 2023, 13, 1530-1538

Unveiling the inhibitory mechanism of aureusidin targeting xanthine oxidase by multi-spectroscopic methods and molecular simulations
Pei He, Haiqi Xu, Can Yang, Dehong Yu, Yi Liu, Jiana Du and Yanfang Li
RSC Adv., 2023, 13, 1606-1616

CO2 free production of ethylene oxide via liquid phase epoxidation of ethylene using niobium oxide incorporated mesoporous silica material as the catalyst
Muhammad Maqbool, Toheed Akhter, Muhammad Faheem, Sohail Nadeem, Chan Ho Park and Asif Mahmood
RSC Adv., 2023, 13, 1779-1786

Silica supported lanthanum trifluoroacetate and trichloroacetate as an efficient and reusable water compatible Lewis acid catalyst for synthesis of 2,4,5-triarylimidazoles via a solvent-free green approach
Dnyaneshwar Purushottam Gholap, Ramdas Huse, Sudarshan Dipake and Machhindra K. Lande
RSC Adv., 2023, 13, 2090-2103

Deep learning for automated size and shape analysis of nanoparticles in scanning electron microscopy
Jonas Bals and Matthias Epple
RSC Adv., 2023, 13, 2795-2802

 

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December 2022 Popular Advances Articles

Welcome to December’s Popular Advances article round up!

Every month we update our 2022 RSC Advances Popular Advances Article Collection to showcase all of the articles selected by our reviewers and handling editors as Popular Advances in 2022. Don’t forget to come back next month to check out our latest Popular articles.

We hope you enjoy reading and as always, all of our articles are open access so you can easily share your favourites online and with your colleagues.

Explore the full collection!

 

Microwave-assisted synthesis, molecular docking studies of 1,2,3-triazole-based carbazole derivatives as antimicrobial, antioxidant and anticancer agents
Dongamanti Ashok, Gugulothu Thara, Bhukya Kiran Kumar, Gundu Srinivas, Dharavath Ravinder, Thumma Vishnu, Madderla Sarasija and Bujji Sushmitha
RSC Adv., 2023, 13, 25-40

Identification of new inhibitors of NS5 from dengue virus using saturation transfer difference (STD-NMR) and molecular docking studies
Asmat Ullah, Atia-tul-Wahab, Peng Gong, Abdul Mateen Khan and M. Iqbal Choudhary
RSC Adv., 2023, 13, 355-369
 

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November 2022 Popular Advances Articles

Welcome to November’s Popular Advances article round up!

Every month we update our 2022 RSC Advances Popular Advances Article Collection to showcase all of the articles selected by our reviewers and handling editors as Popular Advances in 2022. Don’t forget to come back next month to check out our latest Popular articles.

We hope you enjoy reading and as always, all of our articles are open access so you can easily share your favourites online and with your colleagues.

Explore the full collection!

Highly sensitive detection of polyborosiloxane (PBS) hydrolysis with mannitol using electrochemical methodology
Baoliang Liu, Xiaoyang Zhang, Qikun Zhang, Yucheng Sun and Zaijun Lu
RSC Adv., 2022, 12, 31168-31172

Revealing the anisotropic phonon behaviours of layered SnS by angle/temperature-dependent Raman spectroscopy
Xiangnan Gong, Ting Yan, Jue Li, Jie Liu, Hanjun Zou, Bin Zhang, Hong Wu, Zizhen Zhou and Xiaoyuan Zhou
RSC Adv., 2022, 12, 32262-32269

Evaluation of antiviral activity of Carica papaya leaves against SARS-CoV-2 assisted by metabolomic profiling
Amr Adel, Mohamed S. Elnaggar, Amgad Albohy, Ahmed A. Elrashedy, Ahmed Mostafa, Omnia Kutkat, Usama Ramadan Abdelmohsen, Eman Al-Sayed and Mohamed A. Rabeh
RSC Adv., 2022, 12, 32844-32852

Mesoporous acidic polymeric ionic liquids as novel solid acids for catalytic hydrolysis of ketoxime reactions
Shanshan Zhao, Zhengxiang Ma, Peng Cheng, Yanji Wang, Xinqiang Zhao, Qiusheng Yang, Junqi Zhang and Dongsheng Zhang
RSC Adv., 2022, 12, 33276-33283

 

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October 2022 Popular Advances Articles

Welcome to October’s Popular Advances article round up!

Every month we update our 2022 RSC Advances Popular Advances Article Collection to showcase all of the articles selected by our reviewers and handling editors as Popular Advances in 2022. Don’t forget to come back next month to check out our latest Popular articles.

We hope you enjoy reading and as always, all of our articles are open access so you can easily share your favourites online and with your colleagues.

Explore the full collection!

 

Evaluation of mesoporous borosilicate glass–ceramic composites as frits in reference electrodes
Ibrahim H. A. Badr and Osama A. S. Rafe
RSC Adv., 2022,12, 28878-28885

3,4,3′-Tri-O-methylellagic acid as an anticancer agent: in vitro and in silico studies
Andika Pramudya Wardana, Muhammad Ikhlas Abdjan, Nanik Siti Aminah, Mochamad Zakki Fahmi, Imam Siswanto, Alfinda Novi Kristanti, Mirza Ardella Saputra and Yoshiaki Takaya
RSC Adv., 2022,12, 29884-29891

Review on fluorinated nucleoside/non-nucleoside FDA-approved antiviral drugs
Magda M. F. Ismail and Mohammed Salah Ayoup
RSC Adv., 2022,12, 31032-31045

 

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RSC Advances Popular Advances Interview with Abdu Saeed

We are very pleased to introduce Dr Abdu Saeed who is the corresponding author of the RSC Advances article, antibacterial activity of the micro and nanostructures of the optical material tris(8-hydroxyquinoline)aluminum and its application as an antimicrobial coating. This was well received by reviewers and was handpicked by our handling editors to be part of our Popular Advances collection – a big congratulations to all the authors!

Dr Saeed told us more about the work that went into this study and what he hopes to achieve in the future. You can explore other articles in our 2022 Popular Advances online collection here!

 

Meet the Author:

Abdu Saeed was born in Ibb, Yemen, in 1979. After obtaining two degrees in physics (from Ibb University and Taiz University, respectively) he was selected as a teaching assistant at Thamar University. Afterwards, he pursued an MSc and PhD in applied experimental physics at King Abdulaziz University, Saudia Arabia, where he was selected as the best postgraduate student! Nowadays, Dr Saeed works in multidisciplinary fields including energy, electrical properties, nanotechnology, and polymer science. Currently, Dr Saeed and his group are studying the bio applications of the optical material tris(8-hydroxyquinoline)aluminum.

 

Could you briefly explain the focus of your article to the non-specialist and why it is of current interest?
This research focuses mainly on estimating the antibacterial activity of Alq3, but the effect of particle size (micro- and nano- structures) of the Alq3 powders was also investigated. Furthermore, we successfully incorporated this material with polystyrene to form an antibacterial composite for coating purposes.

How big an impact could your results potentially have?
Alq3 is one of the most famous small molecular semiconductors with efficient electroluminescence and fluorescence properties. Since this material was used to manufacture the first OLED, it has been utilized massively in fabricating optoelectrical devices. However, it has not been used in bio applications. Therefore, we think use as an antibacterial coating could bring more interest to Alq3 in bio applications. 

Could you explain the motivation behind this study?
I was studying the toxicity of this material and found two things: Firstly, this material has high toxicity and, when used as a dye for fluorescence bioimaging, the captured images had high fluorescence. These results gave the motivation to utilize this material in new bio applications. Secondly, we spent three months overcoming bacterial contamination in the lab while doing the cell viability experiments. These two things motivated us to study whether Alq3 can be used as an antibacterial agent.

In your opinion, what are the key design considerations for your study?
Alq3 is an attractive and exciting material. It has different crystal structures, and it is considered the most popular organometallic semiconductor in OLED. Its molecular structure has a conjugated π-electron system, which is advantageous for many applications. This material has electroluminescence (EL) and photoluminescence (PL) properties. EL properties make it an excellent material for optoelectronics devices; PL properties make it a good material for optical applications. Its diverse properties and current applications make it an excellent candidate for more investigations into new applications.

Which part of the work towards this paper proved to be most challenging?
We tested the antibacterial activity of the Alq3 samples on seven different human pathogenic bacterial strains representing Gram-positive and Gram-negative bacteria: Escherichia coli ATCC 11775 (EC), Enterococcus faecalis ATCC 29212 (EF), Klebsiella pneumoniae ATCC 13883 (KP), Methicillin-resistant Staphylococcus aureus ATCC 33591 (MRSA), Pseudomonas aeruginosa ATCC 9027 (PA), Staphylococcus aureus ATCC 12600 (SA), and Salmonella Typhimurium ATCC 14028 (ST). Estimating the IC50 for this material against the bacterial strains was the most challenging part of this study.

What aspect of your work are you most excited about at the moment?
We are most excited about using Alq3 in biosensor applications, particularly in bioimaging. We believe that it will be interesting to make modifications, such as using an appropriate material as a surface modifier containing optimized ligands to synthesize Alq3 into a core-shell form. This could further reduce Alq3’s toxicity whilst maintaining its impressive fluorescence.

What is the next step? What work is planned?
We will use what we have achieved to identify and obtain further uses for Alq3. We will study its antifungal activity and incorporate it with suitable polymers for its antifungal tests. Additionally, we hope to check its interaction with different viruses. The first use of Alq3 for bioimaging was by us – we believe there is still much more effort to be made to optimize the use of Alq3 in bioimaging. 

 

Antibacterial activity of the micro and nanostructures of the optical material tris(8-hydroxyquinoline)aluminum and its application as an antimicrobial coating

Graphical abstract: Antibacterial activity of the micro and nanostructures of the optical material tris(8-hydroxyquinoline)aluminum and its application as an antimicrobial coating

 

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RSC Advances Popular Advances Interview with James Knight

We are excited to introduce Dr James Knight, who is the corresponding author of the RSC Advances article, The influence of degree of labelling upon cellular internalisation of antibody-cell penetrating peptide conjugates. The manuscript was well received by reviewers and was handpicked by our handling editors to be part of our Popular Advances collection.

Dr Knight told us more about the work that went into this paper and what he hopes to achieve in the future. You can explore other articles in our 2022 Popular Advances online collection here!

Meet the Author:

Dr James Knight is lecturer in radiochemistry at the School of Natural and Environmental Sciences at Newcastle University. His research surrounds the synthesis and preclinical evaluation of radiopharmaceuticals for imaging and therapeutic applications. Additionally, he is the Degree Programme Director for MSc Drug Chemistry and the lead for radiochemistry within the Discovery of Medicines research theme in the Faculty of Medical Sciences. Interestingly, he also recently co-authored two textbooks on click chemistry and its role in radiochemistry!

The first author, Toni Pringle, is a PhD student who led the research in this paper!

Could you briefly explain the focus of your article to the non-specialist and why it is of current interest?
In the present era of precision medicine, antibodies have emerged as an important class of highly target-specific therapeutic drugs, particularly in oncology, yet their inefficient cellular internalisation limits their scope of application to disease targets situated on the exterior side of the cell membrane. This article is based on research led by PhD student Toni Pringle who modified Herceptin (an antibody used to treat HER2-positive breast and gastric cancers) with a peptide that confers cell-penetrating properties and examined how the extent of this modification affected the uptake of Herceptin in human breast cancer cells, resulting in data that advances our understanding of the cell-internalising properties of these constructs.

How big an impact could your results potentially have?
The results of our study shine a light on the significant influence of a fundamental molecular design parameter – the degree of cell-penetrating peptide labelling. Notably, we found that a radiolabelled analogue of Herceptin modified with five cell-penetrating peptides had uptake in HER2-expressing cells 14.7-fold higher after 48 hours compared to an equivalent analogue with no peptide modification. The scale of this enhancement is exciting when you consider its implications for enhancing the therapeutic index of antibody-drug conjugates, as well as its potential to expand the scope of antibody-based positron emission tomography imaging agents to include disease biomarkers located in the intracellular environment.

Could you explain the motivation behind this study?
The main focus of our research is the development of radiopharmaceuticals that can be used as imaging and/or therapeutic agents for cancer. We are particularly interested in radiopharmaceuticals based on antibody-cell penetrating peptide conjugates (Ab-CPPs) and our motivation in this case was to understand the extent to which cellular internalisation of cancer target-specific Ab-CPP is affected by the degree of peptide labelling. Our group is keen to expand in this area and we felt it was crucial to get a firm handle on this important parameter.

In your opinion, what are the key design considerations for your study?
To allow us to determine the degree of peptide labelling, we decided to use a bioconjugation strategy based on strain-promoted alkyne-azide cycloaddition as this provided a convenient way to measure this parameter by depletion of the alkyne absorbance in the UV region. We also had to think carefully about how to approach the cell-based assays which were fairly complex due to the need to consider several factors, such as the specific activity of the radiolabelled Ab-CPPs, cell numbers and how these would change over the course of the experiment (and how to account for this), the sensitivity of the gamma counter, and of course, radio-protection measures at each stage etc. I must say that Toni did a fabulous job here in the planning and implementation of these experiments.

Which part of the work towards this paper proved to be most challenging?
Working with radioisotopes can be challenging as the agents we put so much effort into making are continually and irretrievably disappearing from the moment we make them! As a result, we have to plan our work very carefully, and often this involves coordinating the activities of several people!

What aspect of your work are you most excited about at the moment?
Radiochemistry and imaging at Newcastle University is thriving and enjoying a period of expansion. The imminent opening of our radiopharmaceutical GMP suite will grant us the ability to readily translate our probes into the clinic, and we have a dedicated network of academics and clinicians supporting us in this endeavour. For me, this is an incredibly exciting prospect!

What is the next step? What work is planned?
We’re taking this forward in two ways. First, we are applying this approach to antibody-drug conjugates to examine the influence of DOL upon therapeutic efficacy in target cell populations. Second, we are developing PET radioligands based on Ab-CPPs to target intracellular biomarkers that arise early in the development of pancreatic cancer to facilitate early detection. In each case, we are applying new, improved cell penetrating peptides. We are looking forward to sharing the results of these investigations soon!

 

The influence of degree of labelling upon cellular internalisation of antibody-cell penetrating peptide conjugates.

Graphical abstract: The influence of degree of labelling upon cellular internalisation of antibody-cell penetrating peptide conjugates

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