Liposomes have been extensively studied and are used in the treatment of several diseases. Liposomes improve the therapeutic efficacy by enhancing drug absorption while avoiding or minimizing rapid degradation and side effects, prolonging the biological half-life and reducing toxicity. The unique feature of liposomes is that they are biocompatible and biodegradable lipids, and are inert and non-immunogenic. Liposomes can compartmentalize and solubilize both hydrophilic and hydrophobic materials. All these properties of liposomes and their flexibility for surface modification to add targeting moieties make liposomes more attractive candidates for use as drug delivery vehicles. There are many novel liposomal formulations that are in various stages of development, to enhance therapeutic effectiveness of new and established drugs that are in preclinical and clinical trials. Recent developments in multimodality imaging to better diagnose disease and monitor treatments embarked on using liposomes as diagnostic tool. Conjugating liposomes with different labeling probes enables precise localization of these liposomal formulations using various modalities such as PET, SPECT, and MRI. In this review, we will briefly review the clinical applications of liposomal formulation and their potential imaging properties.

Pancreatic cancer (PC) has the highest mortality rate amongst all other cancers in both men and women, with a one-year relative survival rate of 20%, and a five-year relative survival rate of 8% for all stages of PC combined. The Whipple procedure, or pancreaticoduodenectomy, can increase survival for patients with resectable PC, however, less than 20% of patients are candidates for surgery at time of presentation. Most of the patients are diagnosed with advanced PC, often with regional and distant metastasis. In these advanced cases, chemotherapy and radiation have shown limited tumor control, and PC continues to be refractory to treatment and results in a poor survival outcome. In recent years, there has been intensive research on checkpoint inhibitor immunotherapy for PC, however, PC is characterized with dense stromal tissue and a tumor microenvironment (TME) that is highly immunosuppressive, which makes immunotherapy less effective. Interestingly, when immunotherapy is combined with radiation therapy (RT) and loco-regional hyperthermia (HT), it has demonstrated enhanced tumor responses. HT improves tumor killing via a variety of mechanisms, targeting both the tumor and the TME. Targeted HT raises the temperature of the tumor and surrounding tissues to 42–43 °C and makes the tumor more immunoresponsive. HT can also modulate the immune system of the TME by inducing and synthesizing heat shock proteins (HSP), which also activate an anti-tumor response. It is well known that HT can enhance RT-induced DNA damage in cancer cells and simultaneously help to oxygenate hypoxic regions. Thus, it is envisaged that combined HT and RT might have immunomodulatory effects in the PC-TME, making PC more responsive to immunotherapies. Moreover, the combined tripartite approach of immunotherapy, RT, and HT could reduce the overall toxicity associated with each individual therapy, while concomitantly enhancing the immunotherapeutic effect of overall individual therapies to treat local and metastatic PC. Thus, the use of a tripartite combinatorial approach could be promising and more efficacious than monotherapy or dual therapy to treat and increase the survival of the PC patients.

Background: Pancreatic cancer (PC) is the fourth-most-deadly cancer in the United States with a 5-year survival rate of only 8%. Unfortunately, only 10–20% of PC patients are candidates for surgery, with the vast majority of patients with locally-advanced disease undergoing chemotherapy and/or radiation therapy (RT). Current treatments are clearly inadequate and novel strategies are crucially required. We investigated a novel tripartite treatment (combination of tumor targeted hyperthermia (HT), radiation therapy (RT), and immunotherapy (IT)) to alter immunosuppressive PC-tumor microenvironment (TME). (2). Methods: In a syngeneic PC murine tumor model, HT was delivered before tumor-targeted RT, by a small animal radiation research platform (SARRP) followed by intraperitoneal injections of cytotoxic T-cell agonist antibody against OX40 (also known as CD134 or Tumor necrosis factor receptor superfamily member 4; TNFRSF4) that can promote T-effector cell activation and inhibit T-regulatory (T-reg) function. (3). Results: Tripartite treatment demonstrated significant inhibition of tumor growth (p < 0.01) up to 45 days post-treatment with an increased survival rate compared to any monotherapy. Flow cytometric analysis showed a significant increase (p < 0.01) in cytotoxic CD8 and CD4+ T-cells in the TME of the tripartite treatment groups. There was no tripartite-treatment-related toxicity observed in mice. (4). Conclusions: Tripartite treatment could be a novel therapeutic option for PC patients.