Tumor Cell Capture Using Platelet-Based and Platelet-Mimicking Modified Human Serum Albumin Submicron Particles.
Xiaotong ZhaoRadostina GeorgievaPichayut RerkshanandanaMoritz HackmannLara-Elena Heil OlaizolaMaxine Müller-de AhnaHans BäumlerPublished in: International journal of molecular sciences (2022)
The co-localization of platelets and tumor cells in hematogenous metastases has long been recognized. Interactions between platelets and circulating tumor cells (CTCs) contribute to tumor cell survival and migration via the vasculature into other tissues. Taking advantage of the interactions between platelets and tumor cells, two schemes, direct and indirect, were proposed to target the modified human serum albumin submicron particles (HSA-MPs) towards tumor cells. HSA-MPs were constructed by the Co-precipitation-Crosslinking-Dissolution (CCD) method. The anti-CD41 antibody or CD62P protein was linked to the HSA-MPs separately via 1-ethyl-3-(-3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) EDC/NHS chemistry. The size of modified HSA-MPs was measured at approximately 1 µm, and the zeta potential was around -24 mV. Anti-CD41-HSA-MPs adhered to platelets as shown by flowcytometry and confocal laser scanning microscopy. In vitro, we confirmed the adhesion of platelets to tumor lung carcinoma cells A549 under shearing conditions. Higher cellular uptake of anti-CD41-HSA-MPs in A549 cells was found in the presence of activated platelets, suggesting that activated platelets can mediate the uptake of these particles. RNA-seq data in the Cancer Cell Lineage Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA) database showed the expression of CD62P ligands in different types of cancers. Compared to the non-targeted system, CD62P-HSA-MPs were found to have higher cellular uptake in A549 cells. Our results suggest that the platelet-based and platelet-mimicking modified HSA-MPs could be promising options for tracking metastatic cancer.
Keyphrases
- single cell
- circulating tumor cells
- rna seq
- human serum albumin
- induced apoptosis
- nk cells
- small cell lung cancer
- papillary thyroid
- emergency department
- squamous cell carcinoma
- escherichia coli
- poor prognosis
- stem cells
- cancer therapy
- cell death
- risk assessment
- climate change
- small molecule
- mesenchymal stem cells
- mass spectrometry
- pseudomonas aeruginosa
- big data
- cell proliferation
- signaling pathway
- long non coding rna
- staphylococcus aureus