Co-delivery of paclitaxel and STAT3 siRNA by a multifunctional nanocomplex for targeted treatment of metastatic breast cancer

Luo, Kaipei; Gao, Yi; Yin, Shaoping; Yao, Yawen; Yu, Hua; Wang, Guangji; Li, Juan

doi:10.1016/j.actbio.2021.07.029

Cited by 38 publications

(23 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Low temperatures (4 °C) usually inhibit the activity of various enzymes, resulting in reduced mitochondrial energy production and thereby reducing cellular uptake. 36,41 After treatment with hypertonic sucrose and chlorpromazine, the cellular uptake of siPD-L1@ PM/DOX@LPs was reduced by 51 and 54%, respectively. Both of these substances disrupt internalization via clathrincoated pits.…”

Section: Resultsmentioning

confidence: 99%

“…Figure D shows that the uptake mechanism of siPD-L1@PM/DOX@LPs was an energy-dependent endocytic process, which was determined by the significantly reduced uptake at a low temperature (4 °C). Low temperatures (4 °C) usually inhibit the activity of various enzymes, resulting in reduced mitochondrial energy production and thereby reducing cellular uptake. , After treatment with hypertonic sucrose and chlorpromazine, the cellular uptake of siPD-L1@PM/DOX@LPs was reduced by 51 and 54%, respectively. Both of these substances disrupt internalization via clathrin-coated pits.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Combinational Chemoimmunotherapy for Breast Cancer by Codelivery of Doxorubicin and PD-L1 siRNA Using a PAMAM-Incorporated Liposomal Nanoplatform

Yao

Wang

et al. 2022

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

Chemoimmunotherapy can synergistically enhance the therapeutic effects and decrease the side effects by a combined method. However, the effective targeted codelivery of various chemotherapeutic agents and siRNAs remains challenging. Although nanomedicine-based chemoimmunotherapy has shown great potential in cancer treatment in recent years, further effort is needed to simplify the nanocarrier designs and maintain their effective functions. Here, we report a simple but robust multifunctional liposomal nanocarrier that contains a pH-sensitive liposome (LP) shell and a dendritic core for tumor-targeted codelivery of programmed cell death ligand 1 (PD-L1) siRNA and doxorubicin (DOX) (siPD-L1@PM/DOX/LPs). siPD-L1@PM/DOX/LPs had a suitable particle size and zeta potential, excellent stability in serum, and pH-sensitive drug release in vitro. They exhibited significant cell proliferation inhibition compared to free DOX and DOX-loaded LPs and could escape endosomes, effectively release siRNA into the cytoplasm of MCF-7 cells, and significantly reduce the PD-L1 expression on tumor cells. In vivo imaging confirmed high accumulation of siPD-L1@PM/DOX/LPs at the tumor site. More importantly, compared with siPD-L1@PM/LPs or DOX alone, siPD-L1@PM/DOX/LPs were more effective in inhibiting tumor growth and activating cytotoxic T cells in vivo. In conclusion, this nanocarrier may hold promise as a codelivery nanoplatform to improve the treatment of various solid tumors.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Combinational Chemoimmunotherapy for Breast Cancer by Codelivery of Doxorubicin and PD-L1 siRNA Using a PAMAM-Incorporated Liposomal Nanoplatform

Yao

Wang

et al. 2022

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

show abstract

“…Moreover, X. Zhou proved that the STAT3/HOTAIR/EZH2 axis may serve as a novel therapeutic target for combination therapy of cisplatin and cetuximab to treat patients with HNSCC with PI3K activation ( 58 ). Luo et al also verified that chemo-gene therapy by combining PTX, the first-line chemotherapeutic drug, with STAT3 siRNA may be a practical strategy to effectively suppress tumor growth and metastasis ( 59 ). Taken together, TSM-1, the PROTAC targeting STAT3 degradation, is expected to be used in combination with first-line therapeutic agents or targeted drugs in clinic to enhance the antitumor effect as well as overcoming drug resistance.…”

Section: Discussionmentioning

confidence: 99%

Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer

Jin¹,

Wu²,

Zhao³

et al. 2022

JCI Insight

View full text Add to dashboard Cite

“…In vitro, STAT3 inhibitor STX-0119 showed cytotoxicity to a variety of pancreatic cancer cell lines, which showed weak PD-L1 expression [ 72 ]. It is worth noting that siRNA, despite its disadvantages of poor stability and low cellular uptake, is protected by exosomes for delivery and transport to help it work, and can even be further enhanced in its oncogenic effects by a co-delivery system formed by nanoparticles and conventional chemotherapeutic drugs [ 73 , 74 , 75 ].…”

Section: Stat3 Inhibitors and Cancermentioning

confidence: 99%

STAT3 Inhibitors: A Novel Insight for Anticancer Therapy of Pancreatic Cancer

Jiang

Dong

et al. 2022

Biomolecules

View full text Add to dashboard Cite

The signal transducer and activator of transcription (STAT) is a family of intracellular cytoplasmic transcription factors involved in many biological functions in mammalian signal transduction. Among them, STAT3 is involved in cell proliferation, differentiation, apoptosis, and inflammatory responses. Despite the advances in the treatment of pancreatic cancer in the past decade, the prognosis for patients with pancreatic cancer remains poor. STAT3 has been shown to play a pro-cancer role in a variety of cancers, and inhibitors of STAT3 are used in pre-clinical and clinical studies. We reviewed the relationship between STAT3 and pancreatic cancer and the latest results on the use of STAT3 inhibitors in pancreatic cancer, with the aim of providing insights and ideas around STAT3 inhibitors for a new generation of chemotherapeutic modalities for pancreatic cancer.

show abstract

Co-delivery of paclitaxel and STAT3 siRNA by a multifunctional nanocomplex for targeted treatment of metastatic breast cancer

Cited by 38 publications

References 52 publications

Combinational Chemoimmunotherapy for Breast Cancer by Codelivery of Doxorubicin and PD-L1 siRNA Using a PAMAM-Incorporated Liposomal Nanoplatform

Combinational Chemoimmunotherapy for Breast Cancer by Codelivery of Doxorubicin and PD-L1 siRNA Using a PAMAM-Incorporated Liposomal Nanoplatform

Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer

STAT3 Inhibitors: A Novel Insight for Anticancer Therapy of Pancreatic Cancer

Contact Info

Product

Resources

About