Subcellular Organelle-Targeted Nanostructured Lipid Carriers for the Treatment of Metastatic Breast Cancer

Wenli Dang; Bin Xing; Xintao Jia; Ying Zhang; Bei Jia; Changxiang Yu; Jiachen He; Ziwei Li; Huihui Li; Zhidong Liu

doi:10.2147/IJN.S413680

Subcellular Organelle-Targeted Nanostructured Lipid Carriers for the Treatment of Metastatic Breast Cancer

Int J Nanomedicine. 2023 Jun 8:18:3047-3068. doi: 10.2147/IJN.S413680. eCollection 2023.

Authors

Wenli Dang^{1

2

3}, Bin Xing^{1

2

3}, Xintao Jia^{1

2

3}, Ying Zhang^{1

2

3}, Bei Jia^{1

2

3}, Changxiang Yu^{1

2

3}, Jiachen He^{1

2

3}, Ziwei Li^{1

2

3}, Huihui Li^{1

2

3}, Zhidong Liu^{1

2

3}

Affiliations

¹ State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.
² Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.
³ Haihe Laboratory of Modern Chinese Medicine, Tianjin, People's Republic of China.

Abstract

Background: Subcellular organelle targeted nano-formulations for cancer treatment are receiving increasing attention owing to their benefits of precise drug delivery, maximized therapeutic index, and reduced off-target side effects. The nucleus and mitochondria, as the main subcellular organelles, are the significant organelles responsible for maintaining cell operation and metabolism. They can be involved in many essential physiological and pathological processes such as cell proliferation, organism metabolism, intracellular transportation, and play a critical role in regulating cell biology. Meanwhile, breast cancer metastasis is one of the leading causes of death in breast cancer patients. With the development of nanotechnology, nanomaterials have been widely used in tumor therapy.

Methods: We designed a subcellular organelle targeted nanostructured lipid carriers (NLC) to deliver paclitaxel (PTX) and gambogic acid (GA) to tumor tissues.

Results: Due to the surface of NLC being modified by subcellular organelle targeted peptide, the PTX and GA co-loaded NLC can accurately release PTX and GA in tumor cells. This property makes NLC able to easy to enter tumor site and target the specific subcellular organelle. The modified NLC can efficiently inhibit the growth of 4T1 primary tumor and lung metastasis, which may be related to the down-regulation of matrix metalloproteinase-9 (MMP-9) and BCL-2 levels, up-regulation of E-cadherin level, and antagonized PTX-induced increase of C-C chemokine ligand 2 (CCL-2) levels by GA. Meanwhile, the synergistic anti-tumor effect of GA and PTX has also been verified in vitro and in vivo experiments.

Conclusion: The subcellular organelle targeted peptide modified PTX+GA multifunctional nano-drug delivery system has a good therapeutic effect on tumors, and this study provides significant insights into the role of different subcellular organelles in inhibiting tumor growth and metastasis and inspires researchers to develop highly effective cancer therapeutic strategies through subcellular organelle targeted drugs.

Keywords: breast cancer metastasis; gambogic acid; mitochondria; nucleus; paclitaxel.

MeSH terms

Breast Neoplasms* / drug therapy
Cell Nucleus
Female
Humans
Lipids
Melanoma, Cutaneous Malignant
Nanostructures*
Paclitaxel / pharmacology

Substances

Paclitaxel
Lipids

Grants and funding

This work was supported by Haihe Laboratory of Modern Chinese Medicine science and technology project (22HHZYSS00005) and the National Administration of Traditional Chinese Medicine Young Qihuang Scholar Project.