TY - JOUR
T1 - An Orthogonally Clickable and Stimuli-Responsive Poly(β-amino ester) for the Co-delivery of Doxorubicin and BCL-2 siRNA
AU - Martí del Rio, Andrea
AU - Sánchez-García, David
N1 - Publisher Copyright:
© 2025 The Authors. Published by American Chemical Society.
PY - 2025/6/13
Y1 - 2025/6/13
N2 - A potent drug delivery system (DDS) based on poly(β-amino ester)s (pBAEs) to tackle multidrug resistance (MDR) in lung cancer by codelivering siRNA targeting antiapoptotic BCL-2 and doxorubicin (DOX) has been prepared. Engineered via strain-promoted azide-alkyne cycloaddition (SPAAC) to attach a tripeptide end-chain moiety and thiol-disulfide exchange to conjugate DOX, the system employs a hydrazone linker for dual pH- and redox-responsive release. This ensures precise tumor targeting with minimal leakage in the circulation. In multidrug-resistant lung cancer cells (GLC-4/ADR), it sharply downregulates BCL-2 expression, amplifying DOX’s therapeutic impact.
AB - A potent drug delivery system (DDS) based on poly(β-amino ester)s (pBAEs) to tackle multidrug resistance (MDR) in lung cancer by codelivering siRNA targeting antiapoptotic BCL-2 and doxorubicin (DOX) has been prepared. Engineered via strain-promoted azide-alkyne cycloaddition (SPAAC) to attach a tripeptide end-chain moiety and thiol-disulfide exchange to conjugate DOX, the system employs a hydrazone linker for dual pH- and redox-responsive release. This ensures precise tumor targeting with minimal leakage in the circulation. In multidrug-resistant lung cancer cells (GLC-4/ADR), it sharply downregulates BCL-2 expression, amplifying DOX’s therapeutic impact.
KW - combination therapy
KW - drug delivery
KW - multidrug-resistance
KW - poly(β-amino ester)
KW - siRNA
KW - stimuli-responsive
KW - strain-promoted azide−alkyne cycloaddition (SPAAC)
KW - thiol−disulfide exchange
UR - http://www.scopus.com/inward/record.url?scp=105007501809&partnerID=8YFLogxK
UR - http://hdl.handle.net/20.500.14342/5352
U2 - 10.1021/acsapm.5c00608
DO - 10.1021/acsapm.5c00608
M3 - Article
AN - SCOPUS:105007501809
SN - 2637-6105
VL - 7
SP - 7013
EP - 7024
JO - ACS Applied Polymer Materials
JF - ACS Applied Polymer Materials
IS - 11
ER -
