Research integrity

Nanotheranostics with a decisive action

"We will look in each instance thoroughly and take a decisive action in consultation with journals and university in each instance as appropriate", Sasha Kabanov, winner of the Lenin Komsomol Prize 1988

Meet a star of Russian and American science, Alexander Kabanov, member of Russian Academy of Sciences, who in 1994 left his home country to revolutionise biomedicine and nanotechnology in USA, and to cure incurable diseases with nanotheranistics: Parkinson’s, cancer, AIDS, you name it. His profile page at the prestigious University of North Carolina at Chapel Hill speaks of “pioneering research in the nanomedicine field“, hundreds of scientific papers and an h-index over 100, “34 United States patents and over 50 foreign patents“, academic research funding of over $54 million, and further $60 million fundraised for his “several companies focusing on therapies of cancers and diseases of the central nervous system“.

Yet some troll has been sneaking dodgy figures into the academician’s papers, who in turn announced “a decisive action“. Good thing that at least one journal, Advanced Functional Materials by Wiley, put its foot down and declared conclusions to be not affected.

Kabanov is an heir of a great scientific dynasty. His father was the Lomonosov Moscow State University (MSU) professor and one of highest-ranking academicians, Viktor Kabanov, a star chemistry researcher in the Soviet Union, winner of highest state awards, who also came from a family of eminent Russian scientists and doctors. As academic genetics go, his son Sasha also made a stellar career at the same MSU, but then in 1991 USSR collapsed, borders opened, and in 1994 Kabanov Jr moved to USA, to the University of Nebraska Medical Center (UNMC). Already as young student, he published many papers with his father, including in the most prestigious Soviet journal, Reports of the Academy of Sciences (Doklady Akademiyi Nauk SSSR). It didn’t hurt that Kabanov Sr acted as its Editor-in-Chief.

I would like to start with a Kabanov paper which was celebrated by a Chapel Hill press release, because it won a grant from from the Eshelman Institute for Innovation. Kabanov and his collaborator Elena Batrakova are both affiliated with the NC Eshelman School of Pharmacy. Both previously graduated at the same MSU in 1983/84, both did their research in Moscow under Kabanov senior (Batrakova was his PhD student), Batrakova also followed Kabanov Jr first to UNMC, and then to Chapel Hill.

Now, Kabanov and Batrakova designed a way to treat Parkinson’s with nanoformulated exosomes. It works in mice like a charm:

Matthew J. Haney , Natalia L. Klyachko , Yuling Zhao , Richa Gupta , Evgeniya G. Plotnikova , Zhijian He , Tejash Patel , Aleksandr Piroyan , Marina Sokolsky , Alexander V. Kabanov , Elena V. Batrakova Exosomes as drug delivery vehicles for Parkinson’s disease therapy Journal of controlled release (2015) doi: 10.1016/j.jconrel.2015.03.033

Fig. 5. Anti-inflammatory effects of exoCAT in PD mouse model. JCR

There is just one problem. These highlighted images of mouse brains were published elsewhere before, by same senior authors, in a different experimental context, but with adjusted brightness:

Yuling Zhao , Matthew J. Haney , Richa Gupta , John P. Bohnsack , Zhijian He , Alexander V. Kabanov , Elena V. Batrakova GDNF-transfected macrophages produce potent neuroprotective effects in Parkinson’s disease mouse model PLoS ONE (2014) doi: 10.1371/journal.pone.0106867

Figure 8. GDNF-transfected macrophages reduce neuro-inflammation in PD mice. PLOS ONE

The PubPeer user Pangio Elongata also noted: “Controls were reused from previous study but not identified in the text.

Fig. 6. Neuroprotective effects of exoCAT in PD mouse model. JCR
Figure 7. Neuroprotective effects of GDNF-transfected macrophages in PD mouse model. PLOS ONE”

Sadly, this is not just a control image reused from a big multi-branch experiment run in parallel (although that wouldn’t be good science either). The animals in the JCR 2015 paper were “C57BL/6 female mice“, those in PLOS One 2014 were “BALB/C female mice“, a completely different mouse strain. No, you can’t mix them up by mistake, one mouse strain is black and the other mice are white.

That control was also used elsewhere before, again with Kabanov and Batrakova on board. This time, a control mouse brain treated with saline buffer from the 2014 PLos One had been paraded as “nanozyme-loaded”:

Natalia L Klyachko , Matthew J Haney , Yuling Zhao , Devika S Manickam , Vivek Mahajan , Poornima Suresh , Shawn D Hingtgen , R Lee Mosley , Howard E Gendelman , Alexander V Kabanov , Elena V Batrakova Macrophages offer a paradigm switch for CNS delivery of therapeutic proteins Nanomedicine (2014) doi: 10.2217/nnm.13.115 

The mice in the 2014 Nanomedicine paper were “C57Bl/6 male mice“, as opposed to the “BALB/C female mice” in 2014 Plos One study. The Kabanov team not only mistook black mice for white, they also apparently couldn’t tell rodent genitals apart. There was even more mouse brain reuse between these two papers, again in different experimental context:

I contacted Kabanov about all that PubPeer evidence, and on 5 June 2021 he informed me by email:

It is very unfortunate but we are very grateful for pointing this out. We will look in each instance thoroughly and take a decisive action in consultation with journals and university in each instance as appropriate

There are more things to look into and to take decisive action upon. Like this:

Alyssa M. Master , Philise N. Williams , Nikorn Pothayee , Nipon Pothayee , Rui Zhang , Hemant M. Vishwasrao , Yuri I. Golovin , Judy S. Riffle , Marina Sokolsky , Alexander V. Kabanov Remote Actuation of Magnetic Nanoparticles For Cancer Cell Selective Treatment Through Cytoskeletal Disruption Scientific Reports (2016) doi: 10.1038/srep33560 

Zygops Histrio: “Figure 4 BT474 panel appear to show the same cells in treatment and no-treatment groups.

Kabanov replied on PubPeer:

Thank you for pointing this out. We are investigating and will take appropriate action.”

PubPeer users found more in that paper, a duplicated flow cytometry plot in Figure S12 framed in red, and even more worrying: a partially cloned FACS plot framed in green.

Do the utterly fake green-framed plots affect the conclusions?

How do things like this in the green box even happen? The authors concluded that all that “has a high impact potential for cancer therapy and could serve as a platform technology in other biomedical applications.

The following was decided to show “good potential as ovarian cancer theranostics“, despite the microscopy images being reused after brightness adjustment and a shift.

Hemant M. Vishwasrao, Alyssa M. Master , Youn Gee Seo , Xinming M. Liu , Nikorn Pothayee , Zhengyuan Zhou, Dongfen Yuan, Michael D. Boska, Tatiana K. Bronich, Richey M. Davis, Judy S. Riffle, Marina Sokolsky-Papkov, Alexander V. Kabanov Luteinizing Hormone Releasing Hormone-Targeted Cisplatin-Loaded Magnetite Nanoclusters for Simultaneous MR Imaging and Chemotherapy of Ovarian Cancer Chemistry of Materials (2016) doi: 10.1021/acs.chemmater.6b00197

Pangio Elongata: “Figure 7 has unexpected similarities in two different cell lines. WT cells at 1hr just less brighter then Cisplatin resistant image at 1h. Same issue for 24 hours image but with slight shift in the image.”

Apparently, this somehow serves to cure ovarian cancer. Also here, Kabanov declared: “We are investigating and will take appropriate action.

Here a study with Kabanov’s former colleague Howard Gendelman from the University of Nebraska Medical Center, where Kabanov worked for many years before moving to Chapel Hill. It serves to cure AIDS, because its nanotechnology “can be used in the clinic to affect the course of HIV-1 infection“, as the authors explain.

Ari S. Nowacek, Shantanu Balkundi , JoEllyn McMillan , Upal Roy , Andrea Martinez-Skinner , R. Lee Mosley , Georgette Kanmogne , Alexander V. Kabanov , Tatiana Bronich , Howard E. Gendelman Analyses of nanoformulated antiretroviral drug charge, size, shape and content for uptake, drug release and antiviral activities in human monocyte-derived macrophages Journal of controlled release (2011) doi: 10.1016/j.jconrel.2010.11.019 

Pangio Elongata, referencing the red boxes: “Some areas on Fig.1 look remarkably similar. Can the authors please explain the similarities between these SEM images of 2 different formulations?”

That journal, issued by the Controlled Release Society (where Kabanov is a fellow since 2018), informed me:

Many thanks for bringing this issue to our attention. The Journal of Controlled Release is following up with the authors directly.

The NC Chapel Hill university never replied. I understand. Kabanov is not just somebody. His institutional profile is awe-inspiring, not just the US achievements, Kabanov’s listed awards include “1988: Lenin Komsomol Prize“, the online CV mentions also and “USSR Medal “For Valiant Labor”, signed by President Mikhail Gorbachev, 1991” also because he was “one of the youngest Doctors of Chemical Sciences ever granted in the nation“. These of course have nothing to do with his father being the president of the chemistry board at the Academy of Sciences of USSR.

No wonder also Kabanov Jr advises the Russian government, as member of Russian Academy of Sciences. He was even celebrated in 2019 with a fictional Russian version of a Nobel Prize by the newspaper Izvestiya, as “the most recognised and authoritative among Russian scientists on the areas of molecular biochemistry and pharmacology“. Kabanov’s institutional profile at Chapel Hill reminds you:

“Kabanov is a recipient of a Megagrant from Russian Government (2010-2014) and professor at MSU where he has established a laboratory with the Megagrant support. He is a member of the Science Council of the Ministry of Education and Science of Russian Federation (2015-present)…”

Original photo: TASS/Izvestiya

And now these rotten figures, what a shame… Oh well, Moscow’s Academy of Sciences is not what it used to be. For example, its current president Alexander Sergeyev recently educated the public that Belarus and Russia must be paid because their forests clean the air from the European greenhouse gasses (but not the Ukrainian forests I presume, with their gay fascist trees). Sergeyev mumbled something about studying wind directions before issuing EU with a bill, and then crawled back up Putin’s behind.

But I digress. At least this Wiley journal stood up to heinous attacks on science and closed the case, after Professor Kabanov provided a picture called “original blot”.

Yuhang Jiang, James M. Fay, Chi‐Duen Poon, Natasha Vinod , Yuling Zhao, Kristin Bullock , Si Qin, Devika S Manickam , Xiang Yi , William A. Banks , Alexander V. Kabanov Nanoformulation of Brain‐Derived Neurotrophic Factor with Target Receptor‐Triggered‐Release in the Central Nervous System Advanced Functional Materials (2018) doi: 10.1002/adfm.201703982 

Now, the colour-boxed gel band similarities in Figure 3k are likely not a problem, because Kabanov explained it was the same blot, stripped. But the other concern of Pangio Elongata, “In addition background on the top panel left part appear to be artificially smooth“, was possibly insufficiently addressed with the raw data Kabanov uploaded. The first image for the phospho-TrkB blot he posted was way too bright, almost without any background signal, and of extremely low resolution.

It is the image on the left, I boosted the signal as much as possible. The arrow indicates what might be a digital splice edge.

Basically, the image Kabanov posted on PubPeer as “original blot” is of much lower resolution that the figure of the same he published 3 years ago. It made no sense. I pointed it out to him. He replied:

The original file stored in the electronic form in our database is here. We will try to identify the machine the image was taken to see if anything with better resolution is taken.

And then Kabanov posted on PubPeer the image on the right, which he described to me as “a file from 2015 experiment of 1.5 MB and should have sufficient resolution“. It is still much too bright, but with slightly higher resolution and more background, the phospho-TrkB staining is not that remarkably clean anymore, look, you even see some unspecific bands. And where did that image suddenly come from?

The journal editor Uta Goebel informed me:

We have carefully checked the images in question, as well as all other images included in the article and cannot find evidence for image/data manipulation in the article.

Attached was her email to Kabanov:

we performed an investigation in accordance with the guidelines of the Committee of Publication Ethics (COPE), in discussion with Wiley’s Integrity in Publishing Group (IPG), also involving our dedicated image check team, double checking all available images within the article.
We concluded that there is no additional action required on the article above. We did not find indications of severe figure or data manipulations and the main conclusions of the article are not affected by the concerns. 

It is indeed an important paper, establishing “Nano-BDNF for treatment for CNS disorders such as stroke, Rett syndrome, and Alzheimer’s disease.” A strange gel cannot affect the conclusions of a breakthrough theranostics therapy which would save the lives of millions of patients.

I asked Goebel if her message to Kabanov means she does not deny that the PubPeer concerns were correct, but decided that those irregularities were neither “severe” nor affected the conclusions. I asked Goebel to correct me if I misunderstood. She didn’t.

Right now, Kabanov works to cure COVID-19, with nanofabrication of course:

“In collaboration with other researchers, Alexander Kabanov’s group in UNC’s Eshelman School of Pharmacy is developing mechanisms to deliver anti-CoV drugs and therapeutic agents directly to the respiratory track. Kabanov’s team uses instruments in the Chapel Hill and Nanofabrication Laboratory to characterize their work.”

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