Trafficking of Gold Nanorods in Breast Cancer Cells: Uptake, Lysosome Maturation, and Elimination

Abstract

Gold nanorods (AuNRs) have been largely investigated driven by their promising potentials in drug delivery, imaging, and photodynamic therapy because of their distinctive physicochemical properties. It is widely known that AuNRs can be taken up by different cells, however, the trafficking of the nanorods in cells are less known. In this work, the behaviors and fate of AuNRs in the human breast cancer cell line MDA-MB-231 were intensively probed by transmission electron microscopy (TEM) with detailed time resolution, together with induced couple plasmon mass spectroscopy (ICP-MS), confocal microscopy, Western blot, and cell viability assay. We reveal that AuNRs enter the classic lysosome maturation through endocytosis and are sequestered in the vesicular system even during cell division. AuNRs can escape from the lysosomes occasionally and the escaped AuNRs are recycled back into the lysosomal system through cytoprotective autophagy. The dilution of AuNRs in cells is mainly attributed to the cell division rather than exocytosis, because expelled AuNRs can be re-endocytosed by the cells. The feature of vesicular restriction guarantees other organelles such as mitochondria and nucleus are exempted from the direct exposure to AuNRs.

One low-dose exposure of gold nanoparticles induces long-term changes in human cells

“…Although there are limitations to analysis of uptake via TEM (slice-by-slice imaging), these qualitative observations have been observed before and quantified in other cases by more sophisticated analyses (36). Occasional lysosomal escape has been reported with positively and negatively charged gold nanorods before, and it was found that PEGylated gold nanospheres escaped into the cytoplasm of macrophages and lung cells (PEG NPs escaped more than citrate NPs in the case of the lung cell study) (36)(37)(38).…”

Gold nanoparticles in breast cancer treatment: Promise and potential pitfalls

“…In another study employing sequential transmission electron microscopy (TEM) of MDA-MB-231 cells, AuNRs were taken up by receptor-mediated endocytosis and formed endocytotic vesicles that evolved into lysosomes and autophagosomes. Reuptake of the eliminated particles was observed after exocytosis [22]. …”

Imaging of Hsp70-positive tumors with cmHsp70.1 antibody-conjugated gold nanoparticles

“…In line with these findings, clusters of nanorods in the perinuclear region were also found to be localized in lysosomes in human mammary carcinoma cell lines. 36 Finally, the quantification of gold nanoparticles that are taken up specifically by tumor cells or tumor cell clusters is important to estimate the amount of nanoparticles that is necessary to improve noninvasive in vivo imaging of tumors in mice and humans. In our setup, we could detect aggregates in perinuclear areas of around 1-2 µm in diameter.…”