Dataset Information

Paclitaxel-loaded ginsenoside Rg3 liposomes for drug-resistant cancer therapy by dual targeting of the tumor microenvironment and cancer cells.

ABSTRACT:

Introduction

Inherent or acquired resistance to paclitaxel (PTX) is a pivotal challenge for chemotherapy treatment of multidrug-resistant (MDR) breast cancer. Although various targeted drug-delivery systems, including nanoparticles and liposomes, are effective for MDR cancer treatment, their efficacy is restricted by immunosuppressive tumor microenvironment (TME).

Methods

Ginsenosides Rg3 was used to formulate unique Rg3-based liposomes loaded with PTX to establish Rg3-PTX-LPs, which were prepared by the thin-film hydration method. The stability of the Rg3-PTX-LPs was evaluated by particle size analysis through dynamic light scattering. The active targeting effect of Rg3-based liposomes was examined in an MCF-7/T xenograft model by an in a vivo imaging system. To evaluate the antitumor activity and mechanism of Rg3-PTX-LP, MTT, apoptosis assays, TAM regulation, and TME remodeling were performed in MCF-7/T cells in vitro and in vivo.

Results

Rg3-PTX-LPs could specifically distribute to MCF7/T cancer cells and TME simultaneously, mainly through the recognition of GLUT-1. The drug resistance reversing capability and in vivo antitumor effect of Rg3-PTX-LPs were significantly improved compared with conventional cholesterol liposomes. The TME remodeling mechanisms of Rg3-PTX-LPs included inhibiting IL-6/STAT3/p-STAT3 pathway activation to repolarize protumor M2 macrophages to antitumor M1 phenotype, suppressing myeloid-derived suppressor cells (MDSCs), decreasing tumor-associated fibroblasts (TAFs) and collagen fibers in TME, and promoting apoptosis of tumor cells. Hence, through the dual effects of targeting tumor cells and TME remodeling, Rg3-PTX-LPs achieved a high tumor inhibition rate of 90.3%.

Conclusion

Our multifunctional Rg3-based liposome developed in the present study offered a promising strategy for rescuing the drug resistance tumor treatment.

SUBMITTER: Zhu Y

PROVIDER: S-EPMC10334248 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Paclitaxel-loaded ginsenoside Rg3 liposomes for drug-resistant cancer therapy by dual targeting of the tumor microenvironment and cancer cells.

Zhu Ying Y Wang Anni A Zhang Shuya S Kim Jisu J Xia Jiaxuan J Zhang Fengxue F Wang Dan D Wang Qi Q Wang Jianxin J

Journal of advanced research 20220924

<h4>Introduction</h4>Inherent or acquired resistance to paclitaxel (PTX) is a pivotal challenge for chemotherapy treatment of multidrug-resistant (MDR) breast cancer. Although various targeted drug-delivery systems, including nanoparticles and liposomes, are effective for MDR cancer treatment, their efficacy is restricted by immunosuppressive tumor microenvironment (TME).<h4>Methods</h4>Ginsenosides Rg3 was used to formulate unique Rg3-based liposomes loaded with PTX to establish Rg3-PTX-LPs, wh ...[more]

PMID: 36167294

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Project description:The inherent flexibility of elastic liposomes (EL) allows them to penetrate the small skin pores and reach the dermal region, making them an optimum candidate for topical drug delivery. Loading chemotherapy in ELs could improve chemotherapy's topical delivery and localise its effect on skin carcinogenic tissues. Chemotherapy-loaded EL can overcome the limitations of conventional administration of chemotherapies and control the distribution to specific areas of the skin. In the current studies, Paclitaxel was utilised to develop Paclitaxel-loaded EL. As an alternative to the conventional manufacturing methods of EL, this study is one of the novel investigations utilising microfluidic systems to examine the potential to enhance and optimise the quality of Els by the microfluidics method. The primary aim was to achieve EL with a size of < 200 nm, high homogeneity, high encapsulation efficiency, and good stability. A phospholipid (DOPC) combined with neutral and anionic edge activators (Tween 80 and sodium taurocholate hydrate) at various lipid-to-edge activator ratios, was used for the manufacturing of the ELs. A preliminary study was performed to study the size, polydispersity (PDI), and stability to determine the optimum microfluidic parameters and lipid-to-edge activator for paclitaxel encapsulation. Furthermore, physiochemical characterisation was performed on the optimised Paclitaxel-loaded EL using a variety of methods, including Dynamic Light Scattering, Fourier Transform Infrared Spectroscopy, Atomic force microscopy, elasticity, encapsulation efficiency, and In vitro release. The results reveal the microfluidics' significant impact in enhancing the EL characteristics of EL, especially small and controllable size, Low PDI, and high encapsulation efficiency. Moreover, the edge activator type and concentration highly affect the EL characteristics. The Tween 80 formulations with optimised concentration provide the most suitable size and higher encapsulation efficiency. The release profile of the formulations showed more immediate release from the EL with higher edge activator concentration and a higher % of the released dug from the Tween 80 formulations.

Dataset Information

Paclitaxel-loaded ginsenoside Rg3 liposomes for drug-resistant cancer therapy by dual targeting of the tumor microenvironment and cancer cells.

Introduction

Methods

Results

Conclusion

Publications

Paclitaxel-loaded ginsenoside Rg3 liposomes for drug-resistant cancer therapy by dual targeting of the tumor microenvironment and cancer cells.

Similar Datasets

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