Engineered Nanoparticles for Enhanced Antitumoral Synergy Between Macrophages and T Cells in the Tumor Microenvironment.

T cells and macrophages have the potential to collaborate to eliminate tumor cells efficiently. Macrophages can eliminate tumor cells through phagocytosis and subsequently activate T cells by presenting tumor antigens. The activated T cells, in turn, can kill tumor cells and redirect tumor-associated macrophages toward an antitumoral M1 phenotype.

A Personalized Cancer Nanovaccine that Enhances T-Cell Responses and Efficacy Through Dual Interactions with Dendritic Cells and T Cells.

Conventional approaches to developing therapeutic cancer vaccines that primarily activate tumor-specific T cells via dendritic cells (DCs) often demonstrate limited efficacy due to the suboptimal activation of these T cells. To address this limitation, here a therapeutic cancer nanovaccine is developed that enhances T cell responses by interacting with both DCs and T cells. The nanovaccine is based on a cancer cell membrane nanoparticle (CCM-MPLA) that utilizes monophosphoryl lipid A (MPLA) as an adjuvant.

Immunomodulation for Tissue Repair and Regeneration.

Various immune cells participate in repair and regeneration following tissue injury or damage, orchestrating tissue inflammation and regeneration processes. A deeper understanding of the immune system's involvement in tissue repair and regeneration is critical for the development of successful reparatory and regenerative strategies. Here we review recent technologies that facilitate cell-based and biomaterial-based modulation of the immune systems for tissue repair and regeneration.

Senescent cancer cell-derived nanovesicle as a personalized therapeutic cancer vaccine.

The development of therapeutic cancer vaccines (TCVs) that provide clinical benefits is challenging mainly due to difficulties in identifying immunogenic tumor antigens and effectively inducing antitumor immunity. Furthermore, there is an urgent need for personalized TCVs because only a limited number of tumor antigens are shared among cancer patients. Several autologous nanovaccines that do not require the identification of immunogenic tumor antigens have been proposed as personalized TCVs.

A Senolytic-Eluting Coronary Stent for the Prevention of In-Stent Restenosis.

The vast majority of drug-eluting stents (DES) elute either sirolimus or one of its analogues. While limus drugs stymie vascular smooth muscle cell (VSMC) proliferation to prevent in-stent restenosis, their antiproliferative nature is indiscriminate and limits healing of the endothelium in stented vessels, increasing the risk of late-stent thrombosis. Oxidative stress, which is associated with vascular injury from stent implantation, can induce VSMCs to undergo senescence, and senescent VSMCs can produce pro-inflammatory cytokines capable of inducing proliferation of neighboring nonsenescent VSMCs.

Nanocomplex-Mediated In Vivo Programming to Chimeric Antigen Receptor-M1 Macrophages for Cancer Therapy.

Chimeric antigen receptor-T (CAR-T) cell immunotherapy has shown impressive clinical outcomes for hematologic malignancies. However, its broader applications are challenged due to its complex ex vivo cell-manufacturing procedures and low therapeutic efficacy against solid tumors. The limited therapeutic effects are partially due to limited CAR-T cell infiltration to solid tumors and inactivation of CAR-T cells by the immunosuppressive tumor microenvironment.

The Senolytic Drug JQ1 Removes Senescent Cells via Ferroptosis.

Background: Ferroptosis is an iron-dependent, non-apoptotic programmed cell death. Cellular senescence contributes to aging and various age-related diseases through the expression of a senescence-associated secretory phenotype (SASP). Senescent cells are often resistant to ferroptosis via increased ferritin and impaired ferritinophagy.

Cardiac-mimetic cell-culture system for direct cardiac reprogramming.

Cardiovascular diseases often cause substantial heart damage and even heart failure due to the limited regenerative capacity of adult cardiomyocytes. The direct cardiac reprogramming of fibroblasts could be a promising therapeutic option for these patients. Although exogenous transcriptional factors can induce direct cardiac reprogramming, the reprogramming efficiency is too low to be used clinically.

Immunomodulatory Lipocomplex Functionalized with Photosensitizer-Embedded Cancer Cell Membrane Inhibits Tumor Growth and Metastasis.

Liposomes are clinically used as drug carriers for cancer therapy; however, unwanted leakage of the encapsulated anticancer drug and poor tumor-targeting efficiency of liposomes may generate toxic side effects on healthy cells and lead to failure of tumor eradication. To overcome these limitations, we functionalized liposomes with a photosensitizer (KillerRed, KR)-embedded cancer cell membrane (CCM). A lipid adjuvant was also embedded in the lipocomplex to promote the anticancer immune response.

Synergistic Oxygen Generation and Reactive Oxygen Species Scavenging by Manganese Ferrite/Ceria Co-decorated Nanoparticles for Rheumatoid Arthritis Treatment.

Poor O supply to the infiltrated immune cells in the joint synovium of rheumatoid arthritis (RA) up-regulates hypoxia-inducible factor (HIF-1α) expression and induces reactive oxygen species (ROS) generation, both of which exacerbate synovial inflammation. Synovial inflammation in RA can be resolved by eliminating pro-inflammatory M1 macrophages and inducing anti-inflammatory M2 macrophages. Because hypoxia and ROS in the RA synovium play a crucial role in the induction of M1 macrophages and reduction of M2 macrophages, herein, we develop manganese ferrite and ceria nanoparticle-anchored mesoporous silica nanoparticles (MFC-MSNs) that can synergistically scavenge ROS and produce O for reducing M1 macrophage levels and inducing M2 macrophages for RA treatment.

M1 Macrophage-Derived Nanovesicles Potentiate the Anticancer Efficacy of Immune Checkpoint Inhibitors.

Cancer immunotherapy modulates immune cells to induce antitumor immune responses. Tumors employ immune checkpoints to evade immune cell attacks. Immune checkpoint inhibitors such as anti-PD-L1 antibody (aPD-L1), which is being used clinically for cancer treatments, can block immune checkpoints so that the immune system can attack tumors.

An Injectable Decellularized Matrix That Improves Mesenchymal Stem Cell Engraftment for Therapeutic Angiogenesis.

Stem cell therapy has great potential for the treatment of ischemic diseases, but poor engraftment of implanted stem cells limits the therapeutic efficacy. Here, we developed an approximately 80 μm injectable decellularized matrix (IDM) to increase the angiogenic efficacy of mesenchymal stem cells by improving the engraftment of the stem cells implanted in to an ischemic tissue. Adhesion of human adipose tissue-derived stem cells (hADSCs) to the IDM enhanced the cell viability and upregulated angiogenic factors in vitro under either cell adhesion-suppressive conditions or hypoxic conditions, which simulated the microenvironment of ischemic tissues.