Uptake of Upconverting Nanoparticles by Breast Cancer Cells: Surface Coating versus the Protein Corona

Abstract

Fluorophores with multifunctional properties known as rare-earth-doped nanoparticles (RENPs) are promising candidates for bioimaging, therapy, and drug delivery. When applied in vivo , these nanoparticles (NPs) have to retain long blood-circulation time, bypass elimination by phagocytic cells, and successfully arrive at the target area. Usually, NPs in a biological medium are exposed to proteins, which form the so-called “protein corona” (PC) around the NPs and influence their targeted delivery and accumulation in cells and tissues. Different surface coatings change the PC size and composition, subsequently deciding the fate of the NPs. Thus, detailed studies on the PC are of utmost importance to determine the most suitable NP surface modification for biomedical use. When it comes to RENPs, these studies are particularly scarce. Here, we investigate the PC composition and its impact on the cellular uptake of citrate-, SiO 2 -, and phospholipid micelle-coated RENPs (LiYF 4 :Yb 3+ ,Tm 3+ ). We observed that the PC of citrate- and phospholipid-coated RENPs is relatively stable and similar in the adsorbed protein composition, while the PC of SiO 2 -coated RENPs is larger and highly dynamic. Moreover, biocompatibility, accumulation, and cytotoxicity of various RENPs in cancer cells have been evaluated. On the basis of the cellular imaging, supported by the inhibition studies, it was revealed that RENPs are internalized by endocytosis and that specific endocytic routes are PC composition dependent. Overall, these results are essential to fill the gaps in the fundamental understanding of the nano-biointeractions of RENPs, pertinent for their envisioned application in biomedicine.

The Coming of Age of Neodymium: Redefining Its Role in Rare Earth Doped Nanoparticles

“…Furthermore, RENPs are chemically stable and are not prone to photo-oxidation because their luminescence arises from the 4f electrons that are not involved in chemical bond formation . RENPs can be synthesized through soft chemistry techniques with functional groups that can be easily modified and then conjugated with biological molecules, ,, making them excellent candidates for sensing, bioimaging, and photoactivated therapies . RENPs are considered nontoxic (though more research is still needed to fully support this statement) .…”

Enhanced drug delivery to cancer cells through a pH-sensitive polycarbonate platform

“…Both these processes contribute to a higher accumulation of nanoparticles inside cancer cells, and indeed the implication of these parameters on the efficacy and targeting of cancer therapeutics has been already exploited. 64,65 In the case of our pH sensitive polycarbonate, the higher nanoparticle uptake in cancer cells and increased exocytosis in normal cells seem to play a key role in enhancing delivery to cancer cells. In essence, taking advantage of the kinetics of nanoparticle accumulation in cancer cells as opposed to normal cells leads to different residence times of the particles within the cells, allowing us to deliver into cancer cells more effectively.…”

Responsive Sensors of Upconversion Nanoparticles

“…, those including protein corona, immune cells, hematological barriers, mucus, and even gastric acids. Though research along this track is still scarce, there has been a report on how protein corona composition may affect the cellular uptake of citrate-, SiO 2 -, and phospholipid micelle-coated UCNPs (LiYF 4 :Yb 3+ ,Tm 3+ ) . Proteins adsorbed on citrate- and phospholipid-coated particles have been found relatively stable and similar in composition, while those for SiO 2 -coated upconversion nanoparticles are larger and highly dynamic.…”

“…Though research along this track is still scarce, there has been a report on how protein corona composition may affect the cellular uptake of citrate-, SiO 2 -, and phospholipid micellecoated UCNPs (LiYF 4 :Yb 3+ ,Tm 3+ ). 52 Proteins adsorbed on citrate-and phospholipid-coated particles have been found relatively stable and similar in composition, while those for SiO 2 -coated upconversion nanoparticles are larger and highly dynamic. The endocytic route for different particles were shown to be dependent on the protein corona composition.…”