10.1021/acsami.6b03977.s001
Maria-Teodora Popescu
Maria-Teodora
Popescu
George Liontos
George
Liontos
Apostolos Avgeropoulos
Apostolos
Avgeropoulos
Efstathia Voulgari
Efstathia
Voulgari
Konstantinos Avgoustakis
Konstantinos
Avgoustakis
Constantinos Tsitsilianis
Constantinos
Tsitsilianis
Injectable
Hydrogel: Amplifying the pH Sensitivity
of a Triblock Copolypeptide by Conjugating the N‑Termini via
Dynamic Covalent Bonding
American Chemical Society
2016
pH window
Triblock Copolypeptide
model drug
extracellular tumor environment
vivo applications
gelling system
Injectable Hydrogel
imine bond
gelation temperature window
pH Sensitivity
5 E 11
polymersome nanocarriers
Soft Matter 2015
Dynamic Covalent Bonding
probe release
Schiff base reaction
triblock copolypeptide
triblock copolypeptide gelator
anticancer drugs
Bz conjugates
2016-06-24 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Injectable_Hydrogel_Amplifying_the_pH_Sensitivity_of_a_Triblock_Copolypeptide_by_Conjugating_the_N_Termini_via_Dynamic_Covalent_Bonding/3469370
We
explore the self-assembly behavior of aqueous solutions of an
amphiphilic, pH-sensitive poly(l-alanine)-<i>b</i>-poly(l-glutamic acid)-<i>b</i>-poly(l-alanine), (A<sub>5</sub>E<sub>11</sub>A<sub>5</sub>) triblock copolypeptide,
end-capped by benzaldehyde through Schiff base reaction. At elevated
concentrations and under physiological pH (7.4) and ionic strength
(0.15M), the bare copolypeptide aqueous solutions underwent a sol–gel
transition after heating and slow cooling thermal treatment, forming
opaque stiff gels due to a hierarchical self-assembly that led to
the formation of β-sheet-based twisted super fibers (Popescu
et al. <i>Soft Matter</i> <b>2015</b>, <i>11</i>, 331–342). The conjugation of the N-termini with benzaldehyde
(Bz) through a Schiff base reaction amplifies the copolypeptide pH-sensitivity
within a narrow pH window relevant for in vivo applications. Specifically,
the dynamic character of the imine bond allowed coupling/decoupling
of the Bz upon switching pH. The presence of Bz conjugates to the
N-termini of the copolypeptide resulted in enhanced packing of the
elementary superfibers into thick and short piles, which inhibited
the ability of the system for gelation. However, partial cleavage
of Bz upon lowering pH to 6.5 prompted recovery of the hydrogel. The
sol–gel transition triggered by pH was reversible, due to the
coupling/decoupling of the benzoic–imine dynamic covalent bonding,
endowing thus the gelling system with injectability. Undesirably,
the gelation temperature window was significantly reduced, which however
can be regulated at physiological temperatures by using a suitable
mixture of the bare and the Bz-conjugated coplypeptide. This triblock
copolypeptide gelator was investigated as a scaffold for the encapsulation
of polymersome nanocarriers, loaded with a hydrophilic model drug,
calcein. The polymersome/polypeptide complex system showed prolonged
probe release in pH 6.5, which is relevant to extracellular tumor
environment, rendering the system potentially useful for sustained
delivery of anticancer drugs locally in the tumor.