PEGylated Paclitaxel Nanomedicine
Meets 3D Confinement: Cytotoxicity and Cell Behaviors
Wenhai Lin#,
Yuanhao Xu#, Xiao Hong, and Stella W. Pang*
#These authors contributed equally
*Corresponding Author
Dr. W. Lin, Dr. Y. Xu, X. Hong and Prof. S. W. Pang
Department of Electrical Engineering
City University of Hong Kong
Hong Kong, China
E-mail: pang@cityu.edu.hk
Keywords: nanomedicine, microwell, paclitaxel, cell migration, 3D
confinement
It is beneficial to investigate the effect of nanomedicines on cancer
cell behaviors on three-dimensional (3D) platforms for evaluating and
developing novel antitumor nanomedicines in vitro .
Two-dimensional flat surface is widely used to study the cytotoxicity of
nanomedicines on cancer cells, and there is little work using 3D
confinement to assess the effect of nanomedicine on cancer cells. In
this work, PEGylated paclitaxel nanoparticles (PEG-PTX NPs) were applied
for the first time to treat nasopharyngeal carcinoma (NPC43) cells in 3D
confinement which consisted of microwells with different sizes and a
glass cover. The cytotoxicity of the small molecule drug paclitaxel
(PTX) and PEG-PTX NPs were studied in microwells with sizes of 50×50,
100×100, and 150×150 μm2 and with covers. After NPC43
cells were treated with PTX and PEG-PTX NPs, the cell migration speed
and cell morphology were analyzed in different microwells without and
with covers. The relationship between the cytotoxicity from drugs, the
size effect from microwells, and cell behaviors were analyzed. These
results not only show the effect of 3D confinement on cytotoxicity of
nanomedicines and cell behaviors, but also provide a novel method to
screen anticancer drugs and evaluate the cell behaviors in vitro .
1. Introduction
Nanoparticles (NPs) are widely used for many applications including
catalysis, medicine, and sensors.[1-9]Nanoparticles applied in medicine, or nanomedicines, can overcome
various limitations of small molecule drugs such as strong
hydrophobicity, poor bioavailability, and big side
effects.[10-20] Some nanomedicines have been
available for clinical use, and many other nanomedicines are under
clinical evaluation.[21, 22] Among these
nanomedicines, two nanomedicines based on paclitaxel (PTX), marketed as
Abraxane and Genexol-PM, are widely used in clinics for treating various
cancers such as ovarian, head and neck, and non-small cell lung
cancers.[22-26] To achieve successful preclinical
evaluation of nanomedicines, three-dimensional (3D) platforms are more
suitable as the common two-dimensional (2D) cell culture platforms on
flat surface cannot mimic the complex 3D microenvironment in
vivo .
To better test the cytotoxicity of small molecule drugs and
nanomedicines in vitro , some 3D platforms were
used.[27-39] Microwells were extensively used in
cancer cell studies including immune cell meditated cancer treatment and
anti-cancer drug response evaluation.[40-42]Microwells have also been used for help cancer cells to form spheroids
to test the cytotoxicity of nanomedicines.[43, 44]However, most of these studies still focused on the collective influence
of nanomedicines on the cancer cell population. Previous works have
revealed a clear dependence of cancer cell susceptibility to treatments
with the microwell sizes.[45, 46] Therefore, it is
important to evaluate the effect of physical confinement by microwells
on the effectiveness of nanomedicines in a single-cell level, such that
the time dependent nanomedicine treatment on individual cancer cell
could be better understood. To the best of our knowledges, this is the
first study using 3D confinement with the cover on the top to evaluate
the cytotoxicity of nanomedicine and cell behaviors after cancer cells
are treated with nanomedicines.