Innovation Delivered
Blood-triggered generation of platinum nanoparticle functions as an anti-cancer agent
Xin Zeng, Jie Sun, Suping Li, Jiyun Shi, Han Gao, Wei Sun Leong, Yiqi Wu, Minghui Li, Chengxin Liu, Ping Li, Jing Kong, Yi-Zhou Wu, Guangjun Nie, Yuming Fu, Gen Zhang
https://doi.org/10.1038/s41467-019-14131-z
Summary
Despite the large amount of research on the effects of metal nanoparticles (NPs) in nature and medicine, there has been very limited application in the clinic due to their potential toxicity, cost, and ethical hurdles of research in humans.
In this Nature Communications article, the authors have discovered that platinum (Pt) nanoparticles (NPs) are generated in vivo in human blood when a patient is treated with cisplatin, a powerful anti-cancer agent. They have shown that the self-assembled Pt NPs form rapidly, accumulate in tumors, and remain in the body for an extended period. Furthermore, the Pt NPs by themselves act as anti-cancer agent, but the tumor inhibitory activity is greatly increased when the nanoparticles are loaded with a chemotherapeutic drug, daunorubicin (DNR). The Daunorubicin loaded nanoparticles appeared to be effective even in daunorubicin-resistant models.
The authors proposed that in vivo-generated metal NPs represent a biocompatible drug delivery platform for chemotherapy resistant tumor treatment.
Results from nanoScan SPECT/CT
Authors have used nanoScan SPECT/CT to create high resolution images to track the tumor targeting dynamics of the nanoparticles in vivo.
Human-derived Pt NPs were labeled with 125-I and 500 μCi 125I-Pt NPs was directly injected into DNR-resistant K562-xenografted nude mice. The images were acquired for 30 min at 1, 4, 24 and 48 h time point.
The radioactive signal accumulated in the tumor regions, peaking at 24 h and remaining apparent at 48 h P.I. (Fig. 4f), indicating that the Pt NPs were efficiently taken up by the tumors.
Figure 4. f NanoScan SPECT/CT imaging of 125I-Pt NPs in DNR-resistant K562 cell-xenografted nude mice (n = 5) at 1, 4, 24 and 48 h after intravenous injection of the NPs. The arrows and dotted circles indicate the tumors. MIP: Maximum Intensity Projection.
Dendritic cell derived exosomes loaded with immunoregulatory cargo reprogram local immune responses and inhibit degenerative bone disease in vivo.
Elashiry, M. et al., Journal of Extracellular Vesicles 9, 1795362 (2020).
doi: 10.1080/20013078.2020.1795362
Summary
This recently published study is the first demonstration of DC exosome-based therapy for a degenerative alveolar bone disease and provides the basis for a novel treatment strategy.
Periodontitis (PD) is a chronic bone disease that affects over 50% of the U.S. population. Severe PD lesions are infiltrated with B cells, macrophages, and dendritic cell (DC) clusters with CD4+T cells. The immune response can be shaped based on the maturation status of DCs, yet no effective immunomodulatory agent for PD has been identified. The goal of the current study was to characterize the immunobiology of DC derived exosome subtypes in vitro and in vivo and their ability to reprogram immune cells responsible for inflammatory bone loss.
The authors have used nanoScan SPECT/CT for imaging of exosome biodistribution in the murine periodontitis model.
Results from nanoScan SPECT/CT
Locally administrated exosomes showed higher affinity and slower clearance from periodontal tissues in the inflammatory, alveolar bone loss model. (A) SPECT CT live animal in vivo imaging of free, In-111 (left) or In-111-labelled, exosomes (right) in mice after the 24h IV administration. (B) Local delivery of free, In-111 (left) or In-111-labelled, exosomes (right) by injection in the palatal gingiva at the right side of maxilla was utilized. (C) Radioactivity in maxilla, relative to the total, when free or bound to DC EXO, was expressed as a percentage determined by using SPECT CT images. (D) Radioactivity in maxilla, relative to the total, when free or bound to DC EXO, was expressed as a percentage, in post-mortem isolated maxilla, determined by a gamma counter. Mice were subjected to ligature placement to induce inflammatory bone loss prior to imaging. Yellow arrows delineate maxilla, white arrows liver, spleen and other non-oral sites.
