Chitosan coated pH/redox-responsive hyaluronic acid micelles for enhanced tumor targeted co-delivery of doxorubicin and siPD-L1

Panpan Song; Zhongxia Lu; Tianze Jiang; Wenwei Han; Xiangyan Chen; Xia Zhao

doi:10.1016/j.ijbiomac.2022.09.245

Chitosan coated pH/redox-responsive hyaluronic acid micelles for enhanced tumor targeted co-delivery of doxorubicin and siPD-L1

Panpan Song
, Zhongxia Lu
, Tianze Jiang
, Wenwei Han
, Xiangyan Chen
, Xia Zhao

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

The complex tumor microenvironment (TME) makes it difficult for single chemotherapy to achieve satisfactory therapeutic effects. Here, chitosan-coated hyaluronic acid micelles (R/C/D@HAssOA) that co-delivers doxorubicin (DOX) and programmed death-ligand 1 small interfering RNA (siPD-L1) are developed to enhance anti-tumor effect by combination of immunotherapy and chemotherapy. The pH/reduction dual-responsive co-delivery micelles R/C/D@HAssOA are spherical particles about 180 nm, and have good drug loading performance, stability, biocompatibility, and TME-responsive drug release properties. The CD44 receptor targeting HA significantly enhances the cellular uptake of DOX and siPD-L1, and siPD-L1 causes the immune infiltration of CD4⁺/CD8⁺ T cells by silencing PD-L1 expression. In vivo studies show that R/C/D@HAssOA exhibits significantly stronger anti-breast cancer effect than that of free DOX and micelles loaded only DOX. Therefore, the dual-stimulus responsive micelles provide a promising strategy for combining chemotherapy and siRNA-based immunotherapy to enhance efficacy.

Original language	English
Pages (from-to)	1078-1091
Number of pages	14
Journal	International Journal of Biological Macromolecules
Volume	222
DOIs	https://doi.org/10.1016/j.ijbiomac.2022.09.245
State	Published - 1 Dec 2022
Externally published	Yes

Keywords

Breast cancer
Dual-stimulus responsiveness
Hyaluronic acid
Immunotherapy
Programmed death-ligand 1 small interfering RNA (siPD-L1)

UN SDGs

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

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10.1016/j.ijbiomac.2022.09.245

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title = "Chitosan coated pH/redox-responsive hyaluronic acid micelles for enhanced tumor targeted co-delivery of doxorubicin and siPD-L1",

abstract = "The complex tumor microenvironment (TME) makes it difficult for single chemotherapy to achieve satisfactory therapeutic effects. Here, chitosan-coated hyaluronic acid micelles (R/C/D@HAssOA) that co-delivers doxorubicin (DOX) and programmed death-ligand 1 small interfering RNA (siPD-L1) are developed to enhance anti-tumor effect by combination of immunotherapy and chemotherapy. The pH/reduction dual-responsive co-delivery micelles R/C/D@HAssOA are spherical particles about 180 nm, and have good drug loading performance, stability, biocompatibility, and TME-responsive drug release properties. The CD44 receptor targeting HA significantly enhances the cellular uptake of DOX and siPD-L1, and siPD-L1 causes the immune infiltration of CD4+/CD8+ T cells by silencing PD-L1 expression. In vivo studies show that R/C/D@HAssOA exhibits significantly stronger anti-breast cancer effect than that of free DOX and micelles loaded only DOX. Therefore, the dual-stimulus responsive micelles provide a promising strategy for combining chemotherapy and siRNA-based immunotherapy to enhance efficacy.",

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author = "Panpan Song and Zhongxia Lu and Tianze Jiang and Wenwei Han and Xiangyan Chen and Xia Zhao",

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year = "2022",

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doi = "10.1016/j.ijbiomac.2022.09.245",

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T1 - Chitosan coated pH/redox-responsive hyaluronic acid micelles for enhanced tumor targeted co-delivery of doxorubicin and siPD-L1

AU - Song, Panpan

AU - Lu, Zhongxia

AU - Jiang, Tianze

AU - Han, Wenwei

AU - Chen, Xiangyan

AU - Zhao, Xia

PY - 2022/12/1

Y1 - 2022/12/1

N2 - The complex tumor microenvironment (TME) makes it difficult for single chemotherapy to achieve satisfactory therapeutic effects. Here, chitosan-coated hyaluronic acid micelles (R/C/D@HAssOA) that co-delivers doxorubicin (DOX) and programmed death-ligand 1 small interfering RNA (siPD-L1) are developed to enhance anti-tumor effect by combination of immunotherapy and chemotherapy. The pH/reduction dual-responsive co-delivery micelles R/C/D@HAssOA are spherical particles about 180 nm, and have good drug loading performance, stability, biocompatibility, and TME-responsive drug release properties. The CD44 receptor targeting HA significantly enhances the cellular uptake of DOX and siPD-L1, and siPD-L1 causes the immune infiltration of CD4+/CD8+ T cells by silencing PD-L1 expression. In vivo studies show that R/C/D@HAssOA exhibits significantly stronger anti-breast cancer effect than that of free DOX and micelles loaded only DOX. Therefore, the dual-stimulus responsive micelles provide a promising strategy for combining chemotherapy and siRNA-based immunotherapy to enhance efficacy.

AB - The complex tumor microenvironment (TME) makes it difficult for single chemotherapy to achieve satisfactory therapeutic effects. Here, chitosan-coated hyaluronic acid micelles (R/C/D@HAssOA) that co-delivers doxorubicin (DOX) and programmed death-ligand 1 small interfering RNA (siPD-L1) are developed to enhance anti-tumor effect by combination of immunotherapy and chemotherapy. The pH/reduction dual-responsive co-delivery micelles R/C/D@HAssOA are spherical particles about 180 nm, and have good drug loading performance, stability, biocompatibility, and TME-responsive drug release properties. The CD44 receptor targeting HA significantly enhances the cellular uptake of DOX and siPD-L1, and siPD-L1 causes the immune infiltration of CD4+/CD8+ T cells by silencing PD-L1 expression. In vivo studies show that R/C/D@HAssOA exhibits significantly stronger anti-breast cancer effect than that of free DOX and micelles loaded only DOX. Therefore, the dual-stimulus responsive micelles provide a promising strategy for combining chemotherapy and siRNA-based immunotherapy to enhance efficacy.

KW - Breast cancer

KW - Dual-stimulus responsiveness

KW - Hyaluronic acid

KW - Immunotherapy

KW - Programmed death-ligand 1 small interfering RNA (siPD-L1)

UR - https://www.scopus.com/pages/publications/85139274332

U2 - 10.1016/j.ijbiomac.2022.09.245

DO - 10.1016/j.ijbiomac.2022.09.245

M3 - 文章

C2 - 36183754

AN - SCOPUS:85139274332

SN - 0141-8130

VL - 222

SP - 1078

EP - 1091

JO - International Journal of Biological Macromolecules

JF - International Journal of Biological Macromolecules

ER -

Chitosan coated pH/redox-responsive hyaluronic acid micelles for enhanced tumor targeted co-delivery of doxorubicin and siPD-L1

Abstract

Keywords

UN SDGs

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