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

5 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

Access to Document

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

Cite this

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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,

day = "13",

doi = "10.1021/acsapm.5c00608",

language = "English",

volume = "7",

pages = "7013--7024",

journal = "ACS Applied Polymer Materials",

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publisher = "American Chemical Society",

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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.

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

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JO - ACS Applied Polymer Materials

JF - ACS Applied Polymer Materials

IS - 11

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

Access to Document

Other files and links

Fingerprint

NanoPan-3D: Development of novel drug-delivery nanocarriers directed to dodge potential drug resistance mechanisms using a 3D crosstalk model of pancreatic adenocarcinoma cells and its associated stroma.

GEMAT: Grup d'Enginyeria de Materials

Contracte Andrea Marti per desenvolupar el projecte predoctoral 'Co-delivery of nucleic acids and anticancer drugs using pBAE functionalised mesoporous silica nanoparticles.'

Cite this

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

Abstract

UN SDGs

Keywords

Access to Document

Other files and links

Fingerprint

Projects

NanoPan-3D: Development of novel drug-delivery nanocarriers directed to dodge potential drug resistance mechanisms using a 3D crosstalk model of pancreatic adenocarcinoma cells and its associated stroma.

GEMAT: Grup d'Enginyeria de Materials

Contracte Andrea Marti per desenvolupar el projecte predoctoral 'Co-delivery of nucleic acids and anticancer drugs using pBAE functionalised mesoporous silica nanoparticles.'

Cite this