skip to primary navigationskip to content
 

Jonathan Powell

Science, technology and analysis of mineral structures in the biomedical field; gastrointestinal absorption and cell processing of nanoparticulate minerals

The Aim: we seek to understand how nanostructured minerals, of either endogenous or exogenous origin, contribute to normal health or pathology, as well as how synthetic analogues can have therapeutic activity. Diseases of interest are (i) cancer and (ii) autoimmune/inflammatory disorders, especially Crohn’s disease.

Endogenous Intestinal Nanoparticles. Regarding gastrointestinal processing, we are investigating how soluble antigen and bacterial fragments (e.g. TLR and NLR ligands) of the intestinal lumen form conjugates with calcium phosphate which then, as nanoparticulate constructs, are shuttled to intestinal immune cells (1). Of particular interest is what benefit this apparently commonplace endogenous process affords the host and how or why it might fail in Crohn’s disease (2).

Nanomineral lessons from Nature. More broadly, our research has shown that endogenous nanomineral forms have some distinct advantages over their soluble counterparts, ranging from reduced toxicity (such as the redox activity of iron) to unique cell uptake and signalling effects. We synthesise ‘bio-inspired’ analogues giving rise, for example, to a new form of oral iron for better tolerated gastrointestinal delivery than commonly used ferrous sulphate (3,4). A focus in our current work is how certain nanominerals might be engineered to skew immune signalling but then dissolve to benign or beneficial soluble minerals thereby limiting their downstream bystander effects. 

The Population and Oral Nanoparticle Exposure. The group also has a long standing interest in population exposure to exogenous nano and micron sized mineral particles via the oral route. In particular we are studying how the intestinal endogenous nanomineral route, described above for calcium phosphate constructs, might be ‘hijacked’ by ingested particles that are derived from a Western lifestyle. Exposure to titanium dioxide pigment particles, for example, is common (5). These particles are not digested and we have shown that some accumulate in the human gut (5) whilst others are absorbed systemically by humans (6). Whether such exposure and uptake has any impact on population health is currently a matter of significant interest in the field.

Silicon. Finally, the group has a strong interest in understanding the biological response to silicates in both particulate and soluble (orthosilicic acid) forms (7).

Analysis and Specialist Skill Sets. In all of our work we draw on our skills in (a) structured mineral synthesis (b) particle sizing (c) microscopy and flow imaging techniques and (d) ICP analysis, as exemplified in the figures shown here.  

Particle Sizing
Assessing particle size distributions correctly relies on a suite of techniques since no single technique can cover the full range. Small biological assemblies or nanoparticles (1 to 70-80 nm) are best determined through dynamic light scattering (A: bovine serum albumin in solution). Larger nanoparticles or polydisperse sub-micron colloids (50 to circa 700 nm) are best measured by Nanoparticle Tracking Analysis (B: size distribution of calcium phosphate colloids) as this technique relies upon direct visualisation of individual particles (C: calcium phosphate colloids). As we progress to larger sizes (200nm – 500 µm), sedimentation becomes a problem but can be addressed by coupling a dispersion unit to the particle sizer and performing Static Light Scattering analyses (D: large amorphous silica particles).

 

Publications 

1. Powell JJ et al. An Endogenous Nanomineral Chaperones Luminal Antigen and Peptidoglycan to Intestinal Immune Cells. Nature Nanotechnology. 2015; 10(4):361-9. doi. 10.1038/nnano.2015.19.

2. Robertson J, Haas CT, Pele LC, Monie T, Hewitt RE and Powell JJ. Failure of Immuno-inhibitory PD-L1 Expression in Intestinal APCs of the Endogenous Nanomineral Pathway in Crohn’s Disease. Scientific Reports. 2016 May 26; 6:26747.

3. Powell JJ, Bruggraber SFA, Faria N, Poots LK, Hondow N, Pennycook TJ, Latunde-Dada GO, Brown AP, Pereira DIA. (2013). A nano-disperse ferritin-core mimetics that efficiently corrects anaemia without luminal iron redox activity. Nanomedicine: nanotechnology, biology and medicine 2014 Jan; S1549-9634(13)00776-4.

4. Pereira DIA, Bruggraber SFA, Faria N, Poots LK, Tagmount MA, Aslam MF, Frazer DM, Vulpe CD, Anderson GJ, Powell JJ. Nanoparticulate iron (III) oxo-hydroxide deliver safe iron that is well absorbed and utilized in humans. Nanomedicine: nanotechnology, biology and medicine. 2014 June 28. S1549-9634(14)00325-6.

5. Powell JJ, Faria N, Thomas-McKay E & Pele LC. Origin and fate of dietary nanoparticles and microparticles in the gastrointestinal tract. Journal of Autoimmunity. 2010. 34, 3, J226-J233.

6. Pele LC, Thoree V, Bruggraber SF, Koller ~D, Thompson RP, Lomer MC, Powell JJ. Pharmaceutical/food grade titanium dioxide particles are absorbed into the bloodstream of human volunteers. Part Fibre Toxicology. 2015; 2; 12:26.

7. Ratcliffe S, Jugdaohsingh R, Vivancos J, Marron A, Deshmukh R, Ma JF, Mitani-Ueno N, Robertson J, Wills J, Boekschoten MV, Müller M, Mawhinney RC, Kinrade SD, Isenring P, Bélanger RR, Powell JJ. Identification of a mammalian silicon transporter. Am J Physiol (Cell Physiol). 2017 May 1;312(5):C550-C561.

Jonathan Powell

Dr Jonathan Powell 

jjp37@cam.ac.uk

Group members: Dr. Nuno Faria, Dr. Ravin Jugdaohsingh, Will Thom, Dr. Rachel Hewitt, Ahmad Ramzi, Carlos Bastos, Dagmar Koller

Plain English

We work with trace elements and mineral structures, especially nanoparticles, trying to identify their benefit to health as part of normal physiology. We also look at how disturbances in these systems can lead to pathology, usually because normal processes fail or because of hijack by imposters. For example, in the intestine- which is our main organ of interest- mineral particles naturally form in huge abundance. They trap fragments of their environment in the process, migrate to immune cells and thus are essential in how our intestines survey their outside world. In Crohn’s disease part of this system fails. Additionally, food additive particles can ‘hijack’ the system and accumulate, failing to function like naturally formed particles. Whether there are health implications of this remains unclear. Finally, we use of all this information to inspire new designs of mineral structures with therapeutic potential. Autoimmune disorders and cancer are diseases of current focus.  

Funding

MRC

Jonathan is accepting PhD students.

Jonathan is also available for consultancy.