Antitumor therapy for breast cancer: Focus on tumor‐associated macrophages and nanosized drug delivery systems

Abstract

Background In breast cancer (BC), tumor‐associated macrophages (TAMs) are an important component of the tumor microenvironment and are closely related to poor prognosis. A growing number of studies have focused on the role of TAMs in BC progression and therapeutic strategies targeting TAMs. As an emerging treatment, the application of nanosized drug delivery systems (NDDSs) in the treatment of BC by targeting TAMs has attracted much attention. Aims This review is to summarize the characteristics and treatment strategies targeting TAMs in BC and to clarify the applications of NDDSs targeting TAMs in the treatment of BC by targeting TAMs. Materials & Methods The existing results related to characteristics of TAMs in BC, BC treatment strategies by targeting TAMs, and the applications of NDDSs in these strategies are described. Through analyzing these results, the advantages and disadvantages of the treatment strategies using NDDSs are discussed, which could provide advices on designing NDDSs for BC treatment. Results TAMs are one of the most prominent noncancer cell types in BC. TAMs not only promote angiogenesis, tumor growth and metastasis but also lead to therapeutic resistance and immunosuppression. Mainly four strategies have been used to target TAMs for BC therapy, which include depleting macrophages, blocking recruitment, reprogramming to attain an anti‐tumor phenotype, and increasing phagocytosis. Since NDDSs can efficiently deliver drugs to TAMs with low toxicity, they are promising approaches for targeting TAMs in tumor therapy. NDDSs with various structures can deliver immunotherapeutic agents and nucleic acid therapeutics to TAMs. In addition, NDDSs can realize combination therapies. Discussion TAMs play a critical role in the progression of BC. An increasing number of strategies have been proposed to regulate TAMs. Compared with free drugs, NDDSs targeting TAMs improve drug concentration, reduce toxicity and realize combination therapies. However, in order to achieve better therapeutic efficacy, there are still some disadvantages that need to be considered in the design of NDDSs. Conclusion TAMs play an important role in the progression of BC, and targeting TAMs is a promising strategy for BC therapy. In particular, NDDSs targeting TAMs have unique advantages and are potential treatments for BC.

Antagonist of CD39 and CD73 potentiate Doxycycline repositioning to induce potent antitumor immune response

“…TAMs play a pivotal role in mediating immune evasion and are responsible for the failure of immunotherapeutic treatments. Thus, strategies targeting repolarization of TAMs to anti-tumor subset have received a great attention [58] [59] [60].Tetracyclines like doxycycline have been explored for their anti-cancer potential in several cancer models [61][62][63] [40]. It is reported to decrease the tumor growth and delay the reoccurrence of tumor in murine models [40].…”

Nanoparticles in tumor microenvironment remodeling and cancer immunotherapy

“…In the TME, macrophages are referred to as tumorassociated macrophages (TAMs), constituting 50% of the tumor mass [70]. The TAMs engage in intricate interactions not only with cancer cells but also with natural killer (NK) cells, T cells, endothelial cells, and fibroblasts.…”

Unveiling the Immune Microenvironment’s Role in Breast Cancer: A Glimpse into Promising Frontiers

“…Additionally, M2-like TAMs support tumor angiogenesis, facilitating the development of new blood vessels to supply nutrients and oxygen to the growing tumor. They also contribute to tissue remodeling, developing a supportive environment for cancer cell invasion and dissemination [102].…”

“…Drugs, metals, and microRNAs (miRNAs) may all be carried by nanoparticles, and they can all cooperate to obstruct TAMs in several different ways. According to the latest research, dextran-coated iron oxide nanoparticles can produce reactive oxygen species (ROS) via the iron oxide-mediated Fenton reaction, which regulates the repolarization of TAMs to M1 macrophages and obstructs the growth of BC [102]. By attracting macrophages to the TAMs and inducing M2 polarization to M1, chemotherapy combined with macrophagerelated treatment might improve the anti-cancer impact [118].…”