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

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.

Keywords: Breast cancer; Chemotherapy; Drug targeting; Inflammation; Nanoparticle; Tumor microenvironment.

Fig. 1

An outline of the endogenous and exogenous sources of cancer-promoting inflammation and the possible formation mechanisms of inflammatory microenvironment. a The endogenous and exogenous stimuli causing cancer-promoting inflammatory reactions are concluded as above; b cancer-promoting inflammation induces tumor cells, inflammatory cells, immune cells and stromal cells to secrete various cytokines, chemokines and growth factors. These cellular mediators, in turn, promote the recruitment and phenotypic alterations of immune cells; c inflammation remodel the tumor tissues and forms a favorable microenvironment for breast cancer cell survival

Fig. 2

Interaction between inflammatory microenvironment and breast cancer development. a Inflammatory conditions induce cells to upregulate inflammatory meditators, which activate signaling transduction networks; b the transcription factors translocate to nucleus and interact with each to enhance relevant gene expression; c activated miRNAs and proteins promote the processes of breast cancer growth, metastasis, resistance, and angiogenesis, including cell proliferation, anti-apoptosis, EMT, ECM degradation, drug efflux and immunosuppression; and d the signaling transduction networks in turn reinforce inflammatory microenvironment for better cancer survival