Radiolabeled Biodistribution of Expansile Nanoparticles: Intraperitoneal Administration Results in Tumor Specific Accumulation

Our plain-English summary of Radiolabeled Biodistribution of Expansile Nanoparticles: Intraperitoneal Administration Results in Tumor Specific Accumulation, by A.H. Colby, J. Kirsch, A.N. Patwa, et al (ACS Nano, 2023).

The study

• Authors: A.H. Colby, J. Kirsch, A.N. Patwa, R. Liu, B. Hollister, W. McCulloch, J.E. Burdette, C.J. Pearce, N.H. Oberliels, Y.L. Colson, K. Liu, M.W. Grinstaff
• Journal: ACS Nano
• Published: 2023;17(3):2212-2221
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Nanoparticle biodistribution in vivo is an essential component to the success of nanoparticle-based drug delivery systems. Previous studies with fluorescently labeled expansile nanoparticles, or "eNPs", demonstrated a high specificity of eNPs to tumors that is achieved through a materials-based targeting strategy. However, fluorescent labeling techniques are primarily qualitative in nature and the gold-standard for quantitative evaluation of biodistribution is through radiolabeling. In this manuscript, we synthesize 14C-labeled eNPs to quantitatively evaluate the biodistribution of these particles in a murine model of intraperitoneal mesothelioma via liquid scintillation counting. The results demonstrate a strong specificity of eNPs for tumors that lasts one to 2 weeks postinjection with an overall delivery efficiency to the tumor tissue of 30% of the injected dose which is congruent with prior reports of preclinical efficacy of the technology. Importantly, the route of administration is essential to the eNP's material-based targeting strategy with intraperitoneal administration leading to tumoral accumulation while, in contrast, intravenous administration leads to rapid clearance via the reticuloendothelial system and low tumoral accumulation. A comparison against nanoparticle delivery systems published over the past decade shows that the 30% tumoral delivery efficiency of the eNP is significantly higher than the 0.7% median delivery efficiency of other systems with sufficient quantitative data to define this metric. These results lay a foundation for targeting intraperitoneal tumors and encourage efforts to explore alternative, nonintravenous routes, of delivery to accelerate the translation of nanoparticle therapies to the clinic.

In plain English

This laboratory study in mice tested an experimental drug-delivery particle; it did not study asbestos exposure. The authors made paclitaxel-loaded expansile nanoparticles (eNPs) labeled with radioactive carbon-14. They injected them into nude mice carrying human MSTO-211H mesothelioma cells in the abdomen, either into the abdominal cavity (intraperitoneally) or into a vein, with three animals per group and time point. After intraperitoneal injection, the tumors held a maximum of 65% of the injected dose at 6 hours and 25% at 1 week, while the spleen, liver and lungs held under 5% up to 1 week. After intravenous injection, under 2% reached the tumors, and accumulation was greatest in the spleen. The authors calculated a tumor delivery efficiency of 30% of the injected dose intraperitoneally versus 0.01% intravenously. They compared this with a 0.7% median for other nanoparticle systems from a 2016 review by Wilhelm et al. The authors concluded the results highlight the need for alternative delivery approaches, while noting that a single data point does not guarantee the approach will succeed.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Animal experiment: biodistribution study of radiolabeled (carbon-14) nanoparticles in tumor-bearing mice, comparing intraperitoneal with intravenous injection, plus a comparison against nanoparticle data previously compiled by Wilhelm et al.
• Who was studied: Nude mice xenografted in the peritoneum with MSTO-211H human mesothelioma tumor cells (an intraperitoneal mesothelioma model). Particles were injected 14 days after xenografting. There were three animals per group and time point: intraperitoneal animals were sacrificed at 2 h, 6 h, 24 h, 7 days and 14 days, and intravenous animals at 2 h, 24 h and 7 days. A pilot of eight nude mice was used to set the timing.
• Exposure: Paclitaxel-loaded (5% payload), carbon-14-labeled expansile nanoparticles (PTX-14C-eNPs), 54 nm in diameter. They were given as a 250 μL dose of 8.63 μCi, either intraperitoneally or intravenously via the tail vein. No asbestos exposure was studied.
• Main results:
  • Intraperitoneal group: tumor accumulation peaked at 65% of the injected dose at 6 hours, was nearly 50% at 24 hours and 25% at 1 week.
  • Intraperitoneal group: the spleen, liver and lungs accumulated less than 5% of the injected dose at any point up to 1 week; about 10% was in the spleen at 2 weeks.
  • Intraperitoneal group: other organs in the peritoneal cavity (kidneys, stomach, intestine, reproductive organs) held less than 2.5% of the injected dose at any time point; serum levels were below the limit of quantification.
  • Intravenous group: particles did not substantially localize to tumors (less than 2% of the injected dose); accumulation was greatest in organs of the reticuloendothelial system, in particular the spleen.
  • Comparing total tissue exposure over time (area under the curve), intraperitoneal administration gave a more than 50-fold increase in tumor accumulation and a nearly 10-fold reduction in reticuloendothelial system accumulation compared with intravenous administration.
  • Tumor delivery efficiency was 30% of the injected dose after intraperitoneal administration versus 0.01% after intravenous administration, described as a 3,000-fold increase. The median for other systems surveyed by Wilhelm et al. was 0.7% of the injected dose.
• The authors' conclusion: The authors concluded that the 3,000-fold difference between intraperitoneal and intravenous delivery highlights the need for alternative approaches to nanoparticle delivery. In their view, the results lay a foundation for targeting intraperitoneal tumors and encourage exploring non-intravenous routes of delivery.
• Limitations the authors state:
  • The authors stated that materials-based targeting rests on a single data point here, which does not guarantee its success, and that additional studies by other researchers are needed.
  • The authors stated that their data are not contemporaneous with the Wilhelm et al. data they compared against, and were plotted together only to facilitate comparison.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelioma.

Related studies

• Pilot-scale production of expansile nanoparticles: Practical methods for clinical scale-up — A.H. Colby, R. Liu, et al. (2021)
• Nanoparticle drug-delivery systems for peritoneal cancers: a case study of the design, characterization and development of the expansile nanoparticle — A.H. Colby, N.H. Oberlies, et al. (2017)
• Paclitaxel-loaded expansile nanoparticles enhance chemotherapeutic drug delivery in mesothelioma 3-dimensional multicellular spheroids — H. Lei, S.C. Hofferberth, et al. (2015)
• Paclitaxel-loaded expansile nanoparticles in a multimodal treatment model of malignant mesothelioma — M.D. Schulz, K.A. Zubris, et al. (2011)
• Nanoparticle tumor localization, disruption of autophagosomal trafficking, and prolonged drug delivery improve survival in peritoneal mesothelioma — R. Liu, A.H. Colby, et al. (2016)
• Two-Step Delivery: Exploiting the Partition Coefficient Concept to Increase Intratumoral Paclitaxel Concentrations In vivo Using Responsive Nanoparticles — A.H. Colby, R. Liu, et al. (2016)

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