Replication Study: Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs

Many solid tumor types, such as pancreatic cancer, have a generally poor prognosis, in part because the delivery of therapeutic regimen is prohibited by pathological abnormalities that block access to tumor vasculature, leading to poor bioavailability. Recent development of tumor penetrating iRGD peptide that is covalently conjugated on nanocarriers’ surface or co-administered with nanocarriers becomes a popular approach for tumor targeting. More importantly, scientists have unlocked an important tumor transcytosis mechanism by which drug carrying nanoparticles directly access solid tumors (without the need of leaky vasculature), thereby allowing systemically injected nanocarriers more abundantly distribute at tumor site with improved efficacy. In this focused review, we summarized the design and implementation strategy for iRGD-mediated tumor targeting. This includes the working principle of such peptide and discussion on patient-specific iRGD effect in vivo, commensurate with the level of key biomarker (i.e. neuropilin-1) expression on tumor vasculature. This highlights the necessity to contemplate the use of a personalized approach when iRGD technology is used in clinic.

In this issue of the JCI, Liu et al. use irinotecan-loaded nanoparticles to treat pancreatic adenocarcinomas in mice. Encapsulating drugs into nanoparticles has distinct advantages: it can improve the pharmacokinetics of the drug, enhance efficacy, and reduce unwanted side effects. A drawback is that the large size of nanoparticles restricts their access to the tumor interior. Liu and colleagues show that the cyclic tumor-penetrating peptide iRGD, reported to be capable of enhancing tumor penetration by drugs, can overcome this limitation to a substantial degree when administered together with the nanoparticles. Pancreatic adenocarcinoma is a challenging malignancy to treat and in desperate need for improved treatments; therefore, advances like this are most welcome.

Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting are vital to this process; it allows readers to assess the reliability of the findings, and repeat or build upon the work of other researchers. The NC3Rs developed the ARRIVE guidelines in 2010 to help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments.Despite widespread endorsement by the scientific community, the impact of the ARRIVE guidelines on the transparency of reporting in animal research publications has been limited. We have revised the ARRIVE guidelines to update them and facilitate their use in practice. The revised guidelines are published alongside this paper. This Explanation and Elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2019, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature.As a new international working groupthe authors of this publication, we have revised the guidelines to update them and facilitate their uptake; the ARRIVE guidelines 2019 are published alongside this paper [13]. We have updated the recommendations in line with current best practice, reorganised the information and classified the items into two sets. The ARRIVE Essential 10 constitute the minimum reporting requirement and the Recommended Set provides further context to the study described. The two sets help authors, journal staff, editors and reviewers use the guidelines in practice, and allow a pragmatic implementation with an initial focus on the most critical issues. Once the Essential 10 are consistently reported in manuscripts, items from the Recommended Set can be added to journal requirements over time until all 21 items are routinely reported in all manuscripts. Full methodology for the revision and the allocation of items into sets is described in the accompanying publication [13].A key aspect of the revision was to develop this Explanation and Elaboration document to provide background and rationale for each of the 21 items of ARRIVE 2019. Here we present additional guidance for each item and subitem, explain the importance of reporting this information in manuscripts that describe animal research, elaborate on what to report, and provide supporting evidence. Each subitem is also illustrated with examples of good reporting from the published literature. Box 1: GlossaryBias: Introduction of a systematic error in the estimated effect of an intervention, caused by inadequacies in the design, conduct, or analysis of an experiment.Effect size: Quantitative measure that estimates the magnitude of differences between groups, or relationships between variables. Experimental unit:Biological entity subjected to an intervention independently of all other units, such that it is possible to assign any two experimental units to different t...