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2017 ; 7
(3
): 703-716
Nephropedia Template TP
Shi B
; Huang K
; Ding J
; Xu W
; Yang Y
; Liu H
; Yan L
; Chen X
Theranostics
2017[]; 7
(3
): 703-716
PMID28255361
show ga
Nowadays, chemotherapy is one of the principal modes of treatment for tumor
patients. However, the traditional formulations of small molecule drugs show
short circulation time, low tumor selectivity, and high toxicity to normal
tissues. To address these problems, a facilely prepared, and pH and reduction
dual-responsive polypeptide nanogel was prepared for selectively intracellular
delivery of chemotherapy drug. As a model drug, doxorubicin (DOX) was loaded into
the nanogel through a sequential dispersion and dialysis technique, resulting in
a high drug loading efficiency (DLE) of 96.7 wt.%. The loading nanogel, defined
as NG/DOX, exhibited a uniform spherical morphology with a mean hydrodynamic
radius of 58.8 nm, pH and reduction dual-triggered DOX release, efficient cell
uptake, and cell proliferation inhibition in vitro. Moreover, NG/DOX exhibited
improved antitumor efficacy toward H22 hepatoma-bearing BALB/c mouse model
compared with free DOX·HCl. Histopathological and immunohistochemical analyses
were implemented to further confirm the tumor suppression activity of NG/DOX.
Furthermore, the variations of body weight, histopathological morphology, bone
marrow cell micronucleus rate, and white blood cell count verified that NG/DOX
showed excellent safety in vivo. With these excellent properties in vitro and in
vivo, the pH and reduction dual-responsive polypeptide nanogel exhibits great
potential for on-demand intracellular delivery of antitumor drug, and holds good
prospect for future clinical application.
free
free
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