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Role of inflammatory microenvironment: potential implications for improved breast cancer nano-targeted therapy

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Abstract

Tumor cells, inflammatory cells and chemical factors work together to mediate complex signaling networks, which forms inflammatory tumor microenvironment (TME). The development of breast cancer is closely related to the functional activities of TME. This review introduces the origins of cancer-related chronic inflammation and the main constituents of inflammatory microenvironment. Inflammatory microenvironment plays an important role in breast cancer growth, metastasis, drug resistance and angiogenesis through multifactorial mechanisms. It is suggested that inflammatory microenvironment contributes to providing possible mechanisms of drug action and modes of drug transport for anti-cancer treatment. Nano-drug delivery system (NDDS) becomes a popular topic for optimizing the design of tumor targeting drugs. It is seen that with the development of therapeutic approaches, NDDS can be used to achieve drug-targeted delivery well across the biological barriers and into cells, resulting in superior bioavailability, drug dose reduction as well as off-target side effect elimination. This paper focuses on the review of modulation mechanisms of inflammatory microenvironment and combination with nano-targeted therapeutic strategies, providing a comprehensive basis for further research on breast cancer prevention and control.

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Abbreviations

TME:

Tumor microenvironment

CAFs:

Cancer-associated fibroblasts

IL-6:

Interleukin-6

TNF-α:

Tumor necrosis factor-α

NF-κB:

Nuclear factor-κB

STAT3:

Signal transducer and activator of transcription 3

PGE2:

Prostaglandin E2

HIF1α:

Hypoxia-inducible factor 1α

Th2:

Helper T cell 2

DCs:

Dendritic cells

MDR:

Multi-drug resistance

MDSCs:

Myeloid-derived suppressor cells

Tregs:

Regulatory T cells

ECM:

Extracellular matrix

IFN-γ:

Interferon-γ

VEGF:

Vascular endothelial growth factor

IFP:

Interstitial pressure

LPS:

Lipopolysaccharide

MMPs:

Matrix metalloproteinases

MSCs:

Mesenchymal stem cells

EMT:

Epithelial mesenchymal transition

Wnt:

Wingless/Integrated

IKK:

Inhibitor of κb kinase

TCR:

T cell receptor

Tfh:

Follicular helper T cell

JAK:

Janus kinase

mIL-6R:

Transmembrane IL-6 receptor

SIL-6R:

Soluble IL-6 receptor

Apcs:

Antigen-presenting cells

MAPK:

Mitogen-activated protein kinase

PI3K/AKT:

Phosphoinositide 3-kinase/protein kinase B

TNBC:

Triple-negative breast cancer

miRNA:

MicroRNA

ncRNA:

Non-coding RNA

CSCs:

Cancer stem cells

NK:

Natural killer cell

ADR:

Adriamycin

NDDS:

Nano-drug delivery system

RES:

Reticuloendothelial system

MPS:

Mononuclear phagocytic system

EPR:

Enhanced permeability and retention

DOX:

Doxorubicin

PTX:

Paclitaxel

BBB:

Blood–brain barrier

HER2:

Human epidermal growth factor receptor-2

EGFR:

Epidermal growth factor receptor

HA:

Hyaluronic acid

FR:

Folic acid receptor

FA:

Folic acid

RGD:

Arginine-glycine-aspartic

ER:

Estrogen receptor

PR:

Progesterone receptor

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Acknowledgements

This review was financially supported by the Projects of International Cooperation and Exchanges of National Natural Science Foundation of China (82020108033); the Natural Science Foundation of Guangdong (2019A1515011286); the Open Project funded by Key laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing(2019 Open Project-05); the National Natural Science Foundation of China (81973839).

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  1. Meng Lan and Wenping Lu are the co-first authors.

Authors and Affiliations

  1. College of Pharmacy, Jinan University, Guangzhou, 510632, China

    Meng Lan, Tengteng Zou, Lihong Li, Fengjie Liu & Yu Cai

  2. Guang an’men Hospital China Academy of Chinese Medical Sciences, Beijing, China

    Wenping Lu

  3. College of Life Sciences, Liaoning University, Shenyang, 110036, China

    Tiange Cai

  4. Cancer Research Institute of Jinan University, Guangzhou, China

    Yu Cai

  5. International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), School of Pharmacy, Jinan University, Guangzhou, China

    Yu Cai

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Lan, M., Lu, W., Zou, T. et al. Role of inflammatory microenvironment: potential implications for improved breast cancer nano-targeted therapy. Cell. Mol. Life Sci. 78, 2105–2129 (2021). https://doi.org/10.1007/s00018-020-03696-4

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  • DOI: https://doi.org/10.1007/s00018-020-03696-4

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