An Orthogonally Clickable and Stimuli-Responsive Poly(β-amino ester) for the Co-delivery of Doxorubicin and BCL-2 siRNA

Andrea Martí del Rio; David Sánchez-García

doi:10.1021/acsapm.5c00608

An Orthogonally Clickable and Stimuli-Responsive Poly(β-amino ester) for the Co-delivery of Doxorubicin and BCL-2 siRNA

Andrea Martí del Rio
, David Sánchez-García^*

^*Corresponding author for this work

Research output: Indexed journal article › Article › peer-review

2 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	7013-7024
Number of pages	12
Journal	ACS Applied Polymer Materials
Volume	7
Issue number	11
Early online date	3 Jun 2025
DOIs	https://doi.org/10.1021/acsapm.5c00608
Publication status	Published - 13 Jun 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

combination therapy
drug delivery
multidrug-resistance
poly(β-amino ester)
siRNA
stimuli-responsive
strain-promoted azide−alkyne cycloaddition (SPAAC)
thiol−disulfide exchange

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10.1021/acsapm.5c00608Licence: CC BY-NC-ND

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title = "An Orthogonally Clickable and Stimuli-Responsive Poly(β-amino ester) for the Co-delivery of Doxorubicin and BCL-2 siRNA",

abstract = "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{\textquoteright}s therapeutic impact.",

keywords = "combination therapy, drug delivery, multidrug-resistance, poly(β-amino ester), siRNA, stimuli-responsive, strain-promoted azide−alkyne cycloaddition (SPAAC), thiol−disulfide exchange",

author = "\{Mart{\'i} del Rio\}, Andrea and David S{\'a}nchez-Garc{\'i}a",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors. Published by American Chemical Society.",

year = "2025",

month = jun,

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doi = "10.1021/acsapm.5c00608",

language = "English",

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AU - Martí del Rio, Andrea

AU - Sánchez-García, David

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.

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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

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ER -

An Orthogonally Clickable and Stimuli-Responsive Poly(β-amino ester) for the Co-delivery of Doxorubicin and BCL-2 siRNA

Abstract

UN SDGs

Keywords

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