Polymeric nanoparticles have been widely used as carriers of drugs and bioimaging agents due to their excellent biocompatibility, biodegradability, and structural versatility. The principal application of polymeric nanoparticles in medicine is for cancer therapy, with increased tumor accumulation, precision delivery of anticancer drugs to target sites, higher solubility of pharmaceutical properties and lower systemic toxicity. Recently, the stimuli-responsive polymeric nanoplatforms attracted more and more attention because they can change their physicochemical properties responding to the stimuli conditions, such as low pH, enzyme, redox agents, hypoxia, light, temperature, magnetic field, ultrasound, and so on. Moreover, the unique properties of stimuli-responsive polymeric nanocarriers in target tissues may significantly improve the bioactivity of delivered agents for cancer treatment. This review introduces stimuli-responsive polymeric nanoparticles and their applications in tumor theranostics with the loading of chemical drugs, nucleic drugs and imaging molecules. In addition, we discuss the strategy for designing multifunctional polymeric nanocarriers and provide the perspective for the clinical applications of these stimuli-responsive polymeric nanoplatforms.
Immunotherapy with immune checkpoint blockade (ICB) for glioblastoma (GBM) is promising but its clinical efficacy is seriously challenged by the blood-tumor barrier (BTB) and immunosuppressive tumor microenvironment. Here, anti-programmed death-ligand 1 antibodies (aPD-L1) are loaded into a redox-responsive micelle and the ICB efficacy is further amplified by paclitaxel (PTX)-induced immunogenic cell death (ICD) via a co-encapsulation approach for the reinvigoration of local anti-GBM immune responses. Consequently, the micelles cross the BTB and are retained in the reductive tumor microenvironment without altering the bioactivity of aPD-L1. The ICB efficacy is enhanced by the aPD-L1 and PTX combination with suppression of primary and recurrent GBM, accumulation of cytotoxic T lymphocytes, and induction of long-lasting immunological memory in the orthotopic GBM-bearing mice. The co-encapsulation approach facilitating efficient antibody delivery and combining with chemotherapeutic agent-induced ICD demonstrate that the chemo-immunotherapy might reprogram local immunity to empower immunotherapy against GBM.
Adoptive immunotherapies based on the transfer of functional immune cells hold great promise in treating a wide range of malignant diseases, especially cancers, autoimmune diseases, and infectious diseases. However, manufacturing issues and biological barriers lead to the insufficient population of target-selective effector cells at diseased sites after adoptive transfer, hindering effective clinical translation. The convergence of immunology, cellular biology, and materials science lays a foundation for developing biomaterial-based engineering platforms to overcome these challenges. Biomaterials can be rationally designed to improve ex vivo immune cell expansion, expedite functional engineering, facilitate protective delivery of immune cells in situ, and navigate the infused cells in vivo. Herein, this review presents a comprehensive summary of the latest progress in biomaterial-based strategies to enhance the efficacy of adoptive cell therapy, focusing on function-specific biomaterial design, and also discusses the challenges and prospects of this field.
Rationale: (Myo)fibroblasts are the ultimate effector cells responsible for the production of collagen within alveolar structures, a core phenomenon in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Although (myo)fibroblast-targeted therapy holds great promise for suppressing the progression of IPF, its development is hindered by the limited drug delivery efficacy to (myo)fibroblasts and the vicious circle of (myo)fibroblast activation and evasion of apoptosis.