Magnetic-Nanorod-Mediated Nanowarming with Uniform and Rate-Regulated Heating.

Rewarming cryopreserved samples requires fast heating to avoid devitrification, a challenge previously attempted by magnetic nanoparticle-mediated hyperthermia. Here, we introduce Fe3O4@SiO2 nanorods as the heating elements to manipulate the heating profile to ensure safe rewarming and address the issue of uneven heating due to inhomogeneous particle distribution. The magnetic anisotropy of the nanorods allows their prealignment in the cryoprotective agent (CPA) during cooling and promotes subsequent rapid rewarming in an alternating magnetic field with the same orientation to prevent devitrification. More importantly, applying an orthogonal static magnetic field at a later stage could decelerate heating, effectively mitigating local overheating and reducing CPA toxicity. Furthermore, this orientational configuration offers more substantial heating deceleration in areas of initially higher heating rates, therefore reducing temperature variations across the sample. The efficacy of this method in regulating heating rate and improving rewarming uniformity has been validated using both gel and porcine artery models.

Combining energy-based focal ablation and immune checkpoint inhibitors: preclinical research and clinical trials.

Energy-based focal therapy (FT) uses targeted, minimally invasive procedures to destroy tumors while preserving normal tissue and function. There is strong emerging interest in understanding how systemic immunity against the tumor can occur with cancer immunotherapy, most notably immune checkpoint inhibitors (ICI). The motivation for combining FT and ICI in cancer management relies on the synergy between the two different therapies: FT complements ICI by reducing tumor burden, increasing objective response rate, and reducing side effects of ICI; ICI supplements FT by reducing local recurrence, controlling distal metastases, and providing long-term protection. This combinatorial strategy has shown promising results in preclinical study (since 2004) and the clinical trials (since 2011). Understanding the synergy calls for understanding the physics and biology behind the two different therapies with distinctive mechanisms of action. In this review, we introduce different types of energy-based FT by covering the biophysics of tissue-energy interaction and present the immunomodulatory properties of FT. We discuss the basis of cancer immunotherapy with the emphasis on ICI. We examine the approaches researchers have been using and the results from both preclinical models and clinical trials from our exhaustive literature research. Finally, the challenges of the combinatory strategy and opportunities of future research is discussed extensively.

Tumor therapeutic response monitored by telemetric temperature sensing, a preclinical study on immunotherapy and chemotherapy.

Temperature in the body and the tumor reflects physiological and pathological conditions. A reliable, contactless, and simplistic measurement system can be used for long-term monitoring of disease progression and therapy response. In this study, miniaturized battery-free wireless chips implanted into growing tumors on small animals were used to capture both basal and tumor temperature dynamics. Three preclinical models: melanoma (B16), breast cancer (4T1), and colon cancer (MC-38), were treated with adoptive T cell transfer, AC-T chemotherapy, and anti-PD-1 immunotherapy respectively. Each model presents a distinctive pattern of temperature history dependent on the tumor characteristic and influenced by the administered therapy. Certain features are associated with positive therapeutic response, for instance the transient reduction of body and tumor temperature following adaptive T cell transfer, the elevation of tumor temperature following chemotherapy, and a steady decline of body temperature following anti-PD-1 therapy. Tracking in vivo thermal activity by cost-effective telemetric sensing has the potential of offering earlier treatment assessment to patients without requiring complex imaging or lab testing. Multi-parametric on-demand monitoring of tumor microenvironment by permanent implants and its integration into health information systems could further advance cancer management and reduce patient burden.

Advances of blood cell-based drug delivery systems.

Blood cells, including erythrocytes, leukocytes and platelets are used as drug carriers in a wide range of applications. They have many unique advantages such as long life-span in circulation (especially erythrocytes), target release capacities (especially platelets), and natural adhesive properties (leukocytes and platelets). These properties make blood cell based delivery systems, as well as their membrane-derived carriers, far superior to other drug delivery systems. Despite the advantages, the further development of blood cell-based delivery systems was hindered by limitations in the source, storage, and mass production. To overcome these problems, synthetic biomaterials that mimic blood cell and nanocrystallization of blood cells have been developed and may represent the future direction for blood cell membrane-based delivery systems. In this paper, we review recent progress of the rising blood cell-based drug delivery systems, and also discuss their challenges and future tendency of development.