Biomaterials Science Blog

Sherlock Holmes solves mysterious cases often by identifying footprints and odor left by the suspects at the crime scenes. Scientists are now trying to trap notoriously rare circulating tumor cells (CTCs) in the bloodstream by imprinting their unique topologies and residual biomolecules for efficient early tumor detection.  

The presence of CTCs is a dangerous signal for tumor progression, as they leak into the blood stream from the primary tumor and could potentially invade to other organs, causing metastasis. Unfortunately, they’re extremely rare and thus hard to identify, which poses great challenges for early tumor diagnosis. In a recent publication in Biomaterials Science, Gao et al from Shanghai Jiao Tong University developed a cell-imprinted biomimetic interface, which could intelligently recognize and efficiently capture CTCs, with an over 55% capture efficiency towards spiked MCF-7 cells, a human breast cancer cell line, from rabbit whole blood samples.

The mechanism behind is the synergy of “lock and key” topological and molecular interactions at the cell-biomaterials interface. Using target CTCs as an imprint template, they created a substrate mimicking their topologies and specific immunoaffinity. By leveraging soft lithography, hierarchical micro/nano-structures of CTCs could be recapitulated on an elastomer substrate (PDMS) to modulate cell adhesion behaviour: cell cytoskeleton staining showed that MCF-7 cells captured on the imprinted surface exhibited abundant filopodia and lamellipodia structures, while they showed an approximately spherical structure on flat substrate, indicating weak topographic interaction. Native proteins originating from CTC’s extracellular matrix (ECM) was anchored in the imprinted substrates providing artificial recognition receptors for selective CTC capture. This is supported by the significantly higher MCF-7 cells capture efficiency on MCF-7 imprinted substrates comparing to HeLa-cell (a human-cervical-cancer cell line) imprinted ones. Anti-EpCAM, a natural antibody, was also introduced to accelerate the CTC-substrate interactions. These interactions turned out to play a decisive role in cell capture, followed by that with plastic receptors.

By recapitulating the topological and chemical microenvironment of CTCs, this biomimetic cell-imprinted substrates demonstrate potential for rare cancer cell capture. Considering the significant roles of tissue ECM stiffness and viscoelasticity in metastasis, and the strong integrin-mediated focal adhesion at the CTCs-biomaterial interface, it might be interesting to incorporate mechanical signals into the interface design in the future for enhanced CTCs capture.

Read the full article for FREE until the 9th October!

Cell-imprinted biomimetic interface for intelligent recognition and efficient capture of CTCs, by Su Gao, Shuangshuang Chen and Qinghua Lu

About the web writer

Zhenwei Ma is currently a Ph.D. candidate in Mechanical Engineering at McGill University. He holds a M.E. degree in Chemical Engineering at McGill University and a B.E. degree in Chemical Engineering from Sichuan University. Find out more about him here.

Thyroid cancer is one of the most common endocrine malignancies, and it is the cause of more deaths than all other endocrine cancers combined. Papillary thyroid cancer, a type of thyroid cancer, is often asymptomatic, but because of the progress of modern diagnostic technology its detection rate has shown a rapid increase in the past decade. It has a lower degree of malignancy than that of other types of thyroid cancers and the tumor growth rate is slow, however, it is still very serious as it can develop throughout the thyroid gland and spread extensively in the body, even spreading to distant organs. The conventional method for treating papillary thyroid cancer is surgery, but this comes with a significant risk of injury. Hence, there is a strong need for non-invasive therapeutics which can be used as an alternative to surgery in the treatment of papillary thyroid cancer.

Recently, mitochondria-targeting nanomaterials have gained major attention as mitochondria are cells’ powerhouse, controls various signaling pathways including apoptosis and necrosis and produce reactive oxygen species (ROS). It is important to mention that increases ROS can cause the proliferation of cancer cells and drug resistance. In this present work, researchers used a mitochondria-targeted and exocytosis inhibition strategy. They used polydopamine-coated gold-silver alloy nanoparticles (Au-Ag@PDA NPs) to target papillary thyroid cancer cells (TPC-1 cells). In order to understand the nano-bio interactions between the nanoparticles and the cancer cells, the authors systematically studied the endocytosis pathway, the subcellular localization, and the cellular responses to the nanoparticles.

The results showed that:

(i)Au-Ag@PDA NPs were internalized through a caveolae-mediated and macropinocytosis pathway, localized in mitochondria and block exocytosis pathway

(ii) This lead to cell cycle arrest in S-phase and this inhibited the cell proliferation

(iii) The TPC-1 cells can survive by an autophagy-mediated method to escape the apoptosis or necrosis

The researchers, using the mitrochondria targeting behavior of the nanoparticles, then carried out photothermal therapy for the enhanced treatment of the papillary thyroid cancer cells. These findings indicate that PDA-coated inorganic nanoparticles have potential in mitrochondria-targeted cancer treatments and, one day, these could be provide an alternative to surgery for patients suffering from papillary thyroid cancer.

Read the full paper for free until the 13th May

Targeting mitochondria with Au–Ag@Polydopamine nanoparticles for papillary thyroid cancer therapy Biomater. Sci., 2019, 7, 1052-1063

About the Web/Blog writer:

Dr. Sudip Mukherjee is a Web Writer for Biomaterials Science. He is currently a Postdoctoral Research Associate at the Rice University. His research is involved in the development of advanced nanomaterials for drug/gene delivery in cancer theranostics, immunomodulatory applications & angiogenesis. He published a total of ~35 research articles/patents. He serves as International Advisory Board Member for ‘Materials Research Express‘, IOP Sciences. He is an associate member (AMRSC) of RSC, UK. He serves as reviewer for several international journals like ChemComm, J Mater Chem A, J Mater Chem B, Journal of Biomedical Nanotechnology, RSC Advances, IOP Nanotechnology, Biofabrication etc.

Contact Email: sudip.mukherjee@rice.edu
Twitter: https://twitter.com/sudip_88