Eylem Seç
Understanding "Bio-nano" Interactions from the Nanoparticles' and Cells' Perspectives
Başlık:
Understanding "Bio-nano" Interactions from the Nanoparticles' and Cells' Perspectives
Yazar:
Yang, Hongrong, author.
ISBN:
9780438147942
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (184 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Advisors: Chung Hang Jonathan Choi.
Özet:
The last decade has witnessed impressive achievements in our understanding of the interactions between cells and nanoparticles (NPs) in the field of "nanomedicine". However, there are still two major problems to be addressed. To start with, most of these investigations analyzed the effects of different physicochemical parameters of NPs on endocytosis at the phenomenological level instead of unveiling the biological mechanism that governs the cellular uptake. Moreover, past mechanistic "bio-nano" investigations typically entailed the use of conventional culture systems that do not adequately account for the effect of extracellular mechanical cues.
We firstly focused on the physicochemical properties of NPs. The effects of NP geometry and receptor targeting on the cellular uptake and intracellular trafficking are systematically explored by using C166 (mouse endothelial) cells and gold nanoparticles (AuNPs) of four different aspect ratios (ARs) from 1 to 7. When coated with poly(ethylene glycol) strands, the cellular uptake of untargeted NPs monotically decreases with AR. Next, AuNPs are functionalized with DNA oligonucleotides to target Class A scavenger receptors expressed by C166 cells. Intriguingly, cellular uptake is maximized at a particular AR: shorter nanorods (AR=2) enter C166 cells more than nanospheres (AR=1) and longer nanorods (AR=4 or AR=7). Strikingly, long targeted nanorods align to the cell membrane in a near-parallel manner followed by rotating by ~90° to enter the cell via a caveolae-mediated pathway. Upon cellular entry, targeted nanorods of all ARs predominantly traffic to the late endosome without progressing to the lysosome.
Next, we considered cellular uptake from not only the NPs' perspective but also the cells' perspective. An experimental set-up is designed to impose defined levels of compressive stress upon C2C12 myoblast cells for systematically investigating the combined effects of nanoparticle size and compressive stress on the cellular uptake and intracellular localization of poly(ethylene glycol)-coated gold nanoparticles (Au-PEG NPs). Upon 140 min of compression, a duration of time insufficient to inflict obvious injury to cells, uptake of Au-PEG NPs smaller than 25 nm by the compressed myoblasts is up to 5-fold higher than that by the uncompressed cells. The optimal compressive stress for maximizing the cellular uptake of sub-25 nm NPs monotonically increases with NP size. With and without compression, the Au-PEG NPs enter C2C12 cells via energy-dependent uptake; they also enter compressed C2C12 cells via clathrin-mediated endocytosis as the major pathway. Upon cellular entry, the Au-PEG NPs more readily reside in the late endosomes or lysosomes of compressed C2C12 cells than uncompressed cells. Results from our experimental set-up yield mechanistic insights into the delivery of NPs to cell types that experience extracellular compression under physiological conditions.
These results provide mechanistic insights into the "bio-nano" interactions from the dual perspectives of materials and cells, revealing the interplay between cellular biomechanics and intracellular trafficking. They also point to materials design rules for NP-based delivery carriers to cells.
Notlar:
School code: 1307
Tüzel Kişi Ek Girişi:
Mevcut:*
Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(697040.1) | 697040-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
On Order
Liste seç
Bunu varsayılan liste yap.
Öğeler başarıyla eklendi
Öğeler eklenirken hata oldu. Lütfen tekrar deneyiniz.
:
Select An Item
Data usage warning: You will receive one text message for each title you selected.
Standard text messaging rates apply.