Evidence map›Paper›PMID 38309054›Full record

ArticleBiomaterials2024

Camptothesome-based combination nanotherapeutic regimen for improved colorectal cancer immunochemotherapy.

Zhiren Wang, Wenpan Li, Yanhao Jiang, Tuyen Ba Tran, Jinha Chung, Minhyeok Kim, Aaron James Scott, Jianqin Lu

Open access · greenAbstract read
In one paragraph

Article in Biomaterials, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
3.0field-weighted citation impact, top 9% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 16 citations in OpenAlex.

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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

8 authors at 1 institution in 1 country.

Zhiren WangSkaggs Pharmaceutical Sciences Center, Department of Pharmacology & Toxicology, R. Ken Coit College of Pharmacy, The University of Arizona, Tucson, AZ, 85721, United States.
Wenpan LiSkaggs Pharmaceutical Sciences Center, Department of Pharmacology & Toxicology, R. Ken Coit College of Pharmacy, The University of Arizona, Tucson, AZ, 85721, United States.
Yanhao JiangSkaggs Pharmaceutical Sciences Center, Department of Pharmacology & Toxicology, R. Ken Coit College of Pharmacy, The University of Arizona, Tucson, AZ, 85721, United States.
Tuyen Ba TranSkaggs Pharmaceutical Sciences Center, Department of Pharmacology & Toxicology, R. Ken Coit College of Pharmacy, The University of Arizona, Tucson, AZ, 85721, United States.
Jinha ChungSkaggs Pharmaceutical Sciences Center, Department of Pharmacology & Toxicology, R. Ken Coit College of Pharmacy, The University of Arizona, Tucson, AZ, 85721, United States.
Minhyeok KimSkaggs Pharmaceutical Sciences Center, Department of Pharmacology & Toxicology, R. Ken Coit College of Pharmacy, The University of Arizona, Tucson, AZ, 85721, United States.
Aaron James ScottClinical and Translational Oncology Program, The University of Arizona Cancer Center, Tucson, AZ, 85721, United States; BIO5 Institute, The University of Arizona, Tucson, AZ, 85721, United States.
Jianqin LuSkaggs Pharmaceutical Sciences Center, Department of Pharmacology & Toxicology, R. Ken Coit College of Pharmacy, The University of Arizona, Tucson, AZ, 85721, United States; BIO5 Institute, The University of Arizona, Tucson, AZ, 85721, United States; Division of Hematology and Oncology, Department of Medicine, College of Medicine, The University of Arizona, Tucson, AZ 85721, United States; Southwest Environmental Health Sciences Center, The University of Arizona, Tucson, 85721, United States. Electronic address: lu6@arizona.edu.
University of Arizona · US

Funding

VITAMIN AP30CA023074 · NCI · UNIVERSITY OF ARIZONA · PI Dan Theodorescu · 1985 to 2026
$110.2M
SOUTHWEST ENVIRONMENTAL HEALTH SCIENCES CENTERP30ES006694 · NIEHS · UNIVERSITY OF ARIZONA · PI DEAN BILLHEIMER · 1994 to 2026
$36.7M
A fortified lipid bilayer platform for improved drug packaging and therapeutic deliveryR35GM147002 · NIGMS · UNIVERSITY OF ARIZONA · PI Jianqin Lu · 2022 to 2026
$1.9M
A Phospholipid-Derived Nanotherapeutic Platform for Improved Colorectal Cancer ImmunochemotherapyR01CA272487 · NCI · UNIVERSITY OF ARIZONA · PI Jianqin Lu · 2023 to 2026
$1.4M
NCI NIH HHS P30 CA023074NCI NIH HHS R01 CA272487NIEHS NIH HHS P30 ES006694NIGMS NIH HHS R35 GM147002
6 · The paper itself

Abstract

Camptothesome is a sphingomyelin-conjugated camptothecin (SM-CSS-CPT) nanovesicle that fortified the therapeutic delivery of CPT in diverse cancer types. To mitigate the Camptothesome-induced IDO1 negative feedback mechanism, we had co-encapsulated, indoximod (IND, IDO1 inhibitor) into Camptothesome using doxorubicin-derived IND (DOX-IND). To maximize the therapeutic potential of DOX-IND/Camptothesome, herein, we first dissected the synergistic drug ratio (DOX-IND/SM-CSS-CPT) via systematical in vitro screening. DOX-IND/Camptothesome with optimal drug ratio synchronized in vivo drug delivery with significantly higher tumor uptake compared to free drugs. This optimum DOX-IND/Camptothesome outperformed the combination of Camptothesome, Doxil and IND or other IDO1 inhibitors (BMS-986205 or epacadostat) in treating mice bearing late-stage MC38 tumors, and combination with immune checkpoint blockade (ICB) enabled it to eradicate 60 % of large tumors. Further, this optimized co-delivery Camptothesome beat Folfox and Folfiri, two first-line combination chemotherapies for colorectal cancer in antitumor efficacy and exhibited no side effects as compared to the severe systemic toxicities associated with Folfox and Folfiri. Finally, we demonstrated that the synergistic DOX-IND/Camptothesome was superior to the combined use of Onivyde + Doxil + IND in curbing the advanced orthotopic CT26-Luc tumors and eliminated 40 % tumors with complete metastasis remission when cooperated with ICB, eliciting stronger anti-CRC immune responses and greater reversal of immunosuppression. These results corroborated that with precise optimal synergistic drug ratio, the therapeutic potential of DOX-IND/Camptothesome can be fully unleased, which warrants further clinical investigation to benefit the cancer patients.

Indexed as

Colorectal NeoplasmsDrug Delivery SystemsAnimalsCell Line, TumorDoxorubicinHumansMicePolyethylene GlycolsDoxorubicinliposomal doxorubicinPolyethylene GlycolsCamptothesomeColorectal cancerImmunochemotherapyIndoleamine 2,3-dioxygenaseIndoximod

Identifiers

PMID38309054
PMCPMC10922823
OpenAlexW4391037665

What OpenQuestion holds

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Registered trials

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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.