Simvastatin-Loaded Polymeric Nanoparticles: Targeting Inflammatory Macrophages for Local Adipose Tissue Browning in Obesity Treatment.

Obesity is defined as chronic, low-grade inflammation within specific tissues. Given the escalating prevalence of obesity among individuals of all ages, obesity has reached epidemic proportions, posing an important public health challenge. Despite significant advancements in treating obesity, conventional approaches remain largely ineffective or involve severe side effects, thus underscoring the pressing need to explore and develop treatment approaches. Targeted and local immunomodulation using nanoparticles (NPs) can influence fat production and utilization processes. Statins, known for their anti-inflammatory properties, show the potential for mitigating obesity-related inflammation. A localized delivery option offers several advantages over oral and parenteral delivery methods. Here, we developed simvastatin (Sim) encapsulated within PLGA NPs (Sim-NP) for localized delivery of Sim to adipose tissues (ATs) for immunomodulation to treat obesity. In vitro experiments revealed the strong anti-inflammatory effects of Sim-NPs, which resulted in enhanced modulation of macrophage (MΦ) polarization and induction of AT browning. We then extended our investigation to an in vivo mouse model of high-fat-diet (HFD)-induced obesity. Sim-NP administration led to the controlled release of Sim within AT, directly impacting MΦ activity and inducing AT browning while inducing weight loss. Our findings demonstrated that Sim-NP administration effectively inhibited the progression of obesity-related inflammation, controlled white fat production, and enhanced AT modulation. These results highlight the potential of Sim-NP as a potent nanotherapy for treating obesity by modulating the immune system.

Injectable hydrogels for personalized cancer immunotherapies.

The field of cancer immunotherapy has shown significant growth, and researchers are now focusing on effective strategies to enhance and prolong local immunomodulation. Injectable hydrogels (IHs) have emerged as versatile platforms for encapsulating and controlling the release of small molecules and cells, drawing significant attention for their potential to enhance antitumor immune responses while inhibiting metastasis and recurrence. IHs delivering natural killer (NK) cells, T cells, and antigen-presenting cells (APCs) offer a viable method for treating cancer. Indeed, it can bypass the extracellular matrix and gradually release small molecules or cells into the tumor microenvironment, thereby boosting immune responses against cancer cells. This review provides an overview of the recent advancements in cancer immunotherapy using IHs for delivering NK cells, T cells, APCs, chemoimmunotherapy, radio-immunotherapy, and photothermal-immunotherapy. First, we introduce IHs as a delivery matrix, then summarize their applications for the local delivery of small molecules and immune cells to elicit robust anticancer immune responses. Additionally, we discuss recent progress in IHs systems used for local combination therapy, including chemoimmunotherapy, radio-immunotherapy, photothermal-immunotherapy, photodynamic-immunotherapy, and gene-immunotherapy. By comprehensively examining the utilization of IHs in cancer immunotherapy, this review aims to highlight the potential of IHs as effective carriers for immunotherapy delivery, facilitating the development of innovative strategies for cancer treatment. In addition, we demonstrate that using hydrogel-based platforms for the targeted delivery of immune cells, such as NK cells, T cells, and dendritic cells (DCs), has remarkable potential in cancer therapy. These innovative approaches have yielded substantial reductions in tumor growth, showcasing the ability of hydrogels to enhance the efficacy of immune-based treatments. STATEMENT OF SIGNIFICANCE: As cancer immunotherapy continues to expand, the mode of therapeutic agent delivery becomes increasingly critical. This review spotlights the forward-looking progress of IHs, emphasizing their potential to revolutionize localized immunotherapy delivery. By efficiently encapsulating and controlling the release of essential immune components such as T cells, NK cells, APCs, and various therapeutic agents, IHs offer a pioneering pathway to amplify immune reactions, moderate metastasis, and reduce recurrence. Their adaptability further shines when considering their role in emerging combination therapies, including chemoimmunotherapy, radio-immunotherapy, and photothermal-immunotherapy. Understanding IHs' significance in cancer therapy is essential, suggesting a shift in cancer treatment dynamics and heralding a novel period of focused, enduring, and powerful therapeutic strategies.