TY - JOUR
T1 - Doxorubicin loaded pH responsive biodegradable ABA-type Amphiphilic PEG-b-aliphatic Polyketal-b-PEG block copolymer for therapy against aggressive murine lymphoma
AU - Hira, Sumit Kumar
AU - Mitra, Kheyanath
AU - Srivastava, Prateek
AU - Singh, Shikha
AU - Vishwakarma, Sambhav
AU - Singh, Ranjeet
AU - Ray, Biswajit
AU - Manna, Partha Pratim
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - A novel ABA-type polyethylene glycol (PEG)-b-polyketal (PK)-b-PEG block copolymer was synthesized via click reactions between the monoazido-monomethoxy-PEG and dialkyne terminated aliphatic polyketal with no carboxylic/amide linkages. Formation of the novel block copolymer was confirmed by 1H NMR, GPC, TGA, and DSC studies. The formed copolymer has shown faster degradation at acidic pH. Self-assembly of this block copolymer (average size 6.2 nm) was assessed by fluorescence study using pyrene as a probe. Doxorubicin loaded block copolymeric micelles (69.9 nm) have shown pH dependent elevated drug release at pH 6.4, indicating its potential as a pH responsive nano-carrier for anticancer therapy. The nano-sized copolymer demonstrated tumoricidal activities against the lymphoma of murine and human origin with significant levels of growth inhibition and apoptosis. Therapy with doxorubicin loaded copolymer reduced the tumor size and augmented the life span of the tumor bearing animals with improved histopathological parameters, compared with the untreated control.
AB - A novel ABA-type polyethylene glycol (PEG)-b-polyketal (PK)-b-PEG block copolymer was synthesized via click reactions between the monoazido-monomethoxy-PEG and dialkyne terminated aliphatic polyketal with no carboxylic/amide linkages. Formation of the novel block copolymer was confirmed by 1H NMR, GPC, TGA, and DSC studies. The formed copolymer has shown faster degradation at acidic pH. Self-assembly of this block copolymer (average size 6.2 nm) was assessed by fluorescence study using pyrene as a probe. Doxorubicin loaded block copolymeric micelles (69.9 nm) have shown pH dependent elevated drug release at pH 6.4, indicating its potential as a pH responsive nano-carrier for anticancer therapy. The nano-sized copolymer demonstrated tumoricidal activities against the lymphoma of murine and human origin with significant levels of growth inhibition and apoptosis. Therapy with doxorubicin loaded copolymer reduced the tumor size and augmented the life span of the tumor bearing animals with improved histopathological parameters, compared with the untreated control.
KW - Apoptosis
KW - Block copolymer
KW - Doxorubicin
KW - Lymphoma
KW - Micellar self-assembly
UR - http://www.scopus.com/inward/record.url?scp=85075568433&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2019.102128
DO - 10.1016/j.nano.2019.102128
M3 - Article
C2 - 31747622
AN - SCOPUS:85075568433
SN - 1549-9634
VL - 24
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
M1 - 102128
ER -