Evidence map›Paper›PMID 30525443›Full record

ArticleACS nano2019

Improved Efficacy and Reduced Toxicity Using a Custom-Designed Irinotecan-Delivering Silicasome for Orthotopic Colon Cancer.

Xiangsheng Liu, Jinhong Jiang, Ryan Chan, Ying Ji, Jianqin Lu, Yu-Pei Liao, Michael Okene, Joshua Lin, Paulina Lin, Chong Hyun Chang and 7 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ACS nano, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02551991 (A Randomized, Open-label Phase 2 Study of Nanoliposomal Irinotecan), which is not on this map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02551991 phase2completednot on this map

A Randomized, Open-label Phase 2 Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-Paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma

TypeinterventionalSponsorIpsenRan2015 to 2021Enrolled56ConditionsPancreatic CancerArmsnal-IRI, 5 fluorouracil, Leucovorin, Oxaliplatin
3 · Its place in the literature

Who cites it

53 citing papers in PubMed.

  1. Review
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  19. Article
  20. Multifunctional CaCOJournal of nanobiotechnology · 2023
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Xiangsheng LiuDivision of Nanomedicine, Department of Medicine , University of California , Los Angeles , California 90095 , United States.ORCID 0000-0002-5719-2838
Jinhong JiangCenter for Environmental Implications of Nanotechnology, California NanoSystems Institute , University of California , Los Angeles , California 90095 , United States.
Ryan ChanDivision of Nanomedicine, Department of Medicine , University of California , Los Angeles , California 90095 , United States.
Ying JiDivision of Nanomedicine, Department of Medicine , University of California , Los Angeles , California 90095 , United States.
Jianqin LuDivision of Nanomedicine, Department of Medicine , University of California , Los Angeles , California 90095 , United States.ORCID 0000-0002-5877-619X
Yu-Pei LiaoDivision of Nanomedicine, Department of Medicine , University of California , Los Angeles , California 90095 , United States.
Michael OkeneDivision of Nanomedicine, Department of Medicine , University of California , Los Angeles , California 90095 , United States.
Joshua LinDivision of Nanomedicine, Department of Medicine , University of California , Los Angeles , California 90095 , United States.
Paulina LinDivision of Nanomedicine, Department of Medicine , University of California , Los Angeles , California 90095 , United States.
Chong Hyun ChangCenter for Environmental Implications of Nanotechnology, California NanoSystems Institute , University of California , Los Angeles , California 90095 , United States.
Xiang WangCenter for Environmental Implications of Nanotechnology, California NanoSystems Institute , University of California , Los Angeles , California 90095 , United States.
Ivanna TangDivision of Nanomedicine, Department of Medicine , University of California , Los Angeles , California 90095 , United States.
Emily ZhengDivision of Nanomedicine, Department of Medicine , University of California , Los Angeles , California 90095 , United States.
Waveley QiuDivision of Nanomedicine, Department of Medicine , University of California , Los Angeles , California 90095 , United States.
Zev A WainbergDepartment of Medicine , University of California , Los Angeles , California 90095 , United States.
Andre E NelDivision of Nanomedicine, Department of Medicine , University of California , Los Angeles , California 90095 , United States.ORCID 0000-0002-5232-4686
Huan MengDivision of Nanomedicine, Department of Medicine , University of California , Los Angeles , California 90095 , United States.ORCID 0000-0001-8844-3938

Funding

UCLA Multifunctional Mesoporous Silica Nanoparticle Platform for Treatment of Pancreas CancerU01CA198846 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DONAHUE, TIMOTHY R, MENG, HUAN · 2015 to 2019
$2.4M
NCI NIH HHS U01 CA198846
6 · The paper itself

Abstract

Irinotecan is a key chemotherapeutic agent for the treatment of colorectal (CRC) and pancreatic (PDAC) cancer. Because of a high incidence of bone marrow and gastrointestinal (GI) toxicity, Onivyde (a liposome) was introduced to provide encapsulated irinotecan (Ir) delivery in PDAC patients. While there is an ongoing clinical trial (NCT02551991) to investigate the use of Onivyde as a first-line option to replace irinotecan in FOLFIRINOX, the liposomal formulation is currently prescribed as a second-line treatment option (in combination with 5-fluorouracil and leucovorin) for patients with metastatic PDAC who failed gemcitabine therapy. However, the toxicity of Onivyde remains a concern that needs to be addressed for use in CRC as well. Our goal was to custom design a mesoporous silica nanoparticle (MSNP) carrier for encapsulated irinotecan delivery in a robust CRC model. This was achieved by developing an orthotopic tumor chunk model in immunocompetent mice. With a view to increase the production volume and to expand the disease applications, the carrier design was improved by using an ethanol exchange method for coating of a supported lipid bilayer (LB) that entraps a protonating agent. The encapsulated protonating agent was subsequently used for remote loading of irinotecan. The excellent irinotecan loading capacity and stability of the LB-coated MSNP carrier, also known as a "silicasome", previously showed improved efficacy and reduced toxicity when compared to an in-house liposomal carrier in a PDAC model. Intravenous injection of the silicasomes in a well-developed orthotopic colon cancer model in mice demonstrated improved pharmacokinetics and tumor drug content over free drug and Onivyde. Moreover, improved drug delivery was accompanied by substantially improved efficacy, increased survival, and reduced bone marrow and GI toxicity compared to the free drug and Onivyde. We also confirmed that the custom-designed irinotecan silicasomes outperform Onivyde in an orthotopic PDAC model. In summary, the Ir-silicasome appears to be promising as a treatment option for CRC in humans based on improved efficacy and the carrier's favorable safety profile.

Indexed as

AnimalsAntineoplastic AgentsCell Line, TumorColonic NeoplasmsIrinotecanMiceMice, Inbred C57BLNanocapsulesSilicon DioxideAntineoplastic AgentsIrinotecanNanocapsulesSilicon Dioxidecolorectal canceririnotecanmesoporous silica nanoparticlesOnivydepancreatic cancersilicasomesupported lipid bilayer

Identifiers

PMID30525443
PMCPMC6554030

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.