Advances in Polymeric Micelles: Responsive and Targeting Approaches for Cancer Immunotherapy in the Tumor Microenvironment

Abstract

In recent years, to treat a diverse array of cancer forms, considerable advancements have been achieved in the field of cancer immunotherapies. However, these therapies encounter multiple challenges in clinical practice, such as high immune-mediated toxicity, insufficient accumulation in cancer tissues, and undesired off-target reactions. To tackle these limitations and enhance bioavailability, polymer micelles present potential solutions by enabling precise drug delivery to the target site, thus amplifying the effectiveness of immunotherapy. This review article offers an extensive survey of recent progress in cancer immunotherapy strategies utilizing micelles. These strategies include responsive and remodeling approaches to the tumor microenvironment (TME), modulation of immunosuppressive cells within the TME, enhancement of immune checkpoint inhibitors, utilization of cancer vaccine platforms, modulation of antigen presentation, manipulation of engineered T cells, and targeting other components of the TME. Subsequently, we delve into the present state and constraints linked to the clinical utilization of polymeric micelles. Collectively, polymer micelles demonstrate excellent prospects in tumor immunotherapy by effectively addressing the challenges associated with conventional cancer immunotherapies.

Keywords: cancer immunotherapy; polymeric micelles; responsive delivery systems; targeted drug delivery; tumor microenvironment.

Figure 1

Micelle responsive and remodeling TME, immunosuppressive cells in the TME and ICIs. Micelle responsive TME contain pH, MMPs: Matrix Metalloproteinases, GSH: Glutathione; ROS: Reactive Oxygen Species. Tumor−associated immunosuppressive cells include TAM: MDSC: Myeloid−Derived Suppressor Cell; Tumor−Associated Macrophages; Treg: Regulatory T Cell; CAF: Cancer−Associated Fibroblast. DC Cell: Dendritic Cells; NK cell: Natural Killer Cell; T cell: Thymus Derived cell. ICIs include PD−L1: Programmed Death Ligand 1; IDO: Indoleamine 2,3 Oxygenase; CTLA−4: Cytotoxic T Lymphocyte Antigen−4; PD−1: Programmed Death Receptor 1.

Figure 2

TME−responsive polymeric micelles in tumor immunotherapy. Polymeric micelles achieve targeted drug release to tumor tissues after intravenous administration by responding to a pH range of 6.5−6.9. MMP−2: Matrix Metalloproteinase−2; GSH: Glutathione; ROS: Reactive Oxygen Species.