Evidence map›Paper›PMID 34094838›Full record

ArticleActa pharmaceutica Sinica. B2021

Escape from abluminal LRP1-mediated clearance for boosted nanoparticle brain delivery and brain metastasis treatment.

Naveed Ullah Khan, Jiang Ni, Xiufeng Ju, Tongtong Miao, Haiyan Chen, Liang Han

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta pharmaceutica Sinica. B, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.0field-weighted citation impact, top 7% 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

31 citing papers in PubMed, 75 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

6 authors at 1 institution in 1 country.

Naveed Ullah KhanJiangsu Key Laboratory of Neuropsychiatric Diseases Research and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Jiang NiJiangsu Key Laboratory of Neuropsychiatric Diseases Research and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Xiufeng JuJiangsu Key Laboratory of Neuropsychiatric Diseases Research and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Tongtong MiaoJiangsu Key Laboratory of Neuropsychiatric Diseases Research and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Haiyan ChenJiangsu Key Laboratory of Neuropsychiatric Diseases Research and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Liang HanJiangsu Key Laboratory of Neuropsychiatric Diseases Research and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China.
Soochow University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Breast cancer brain metastases (BCBMs) are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth. Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable blood‒brain barrier (BBB). Accumulation studies prove that low density lipoprotein receptor-related protein 1 (LRP1) is promising target for BBB transcytosis. However, as the primary clearance receptor for amyloid beta and tissue plasminogen activator, LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics. Matrix metalloproteinase-1 (MMP1) is highly enriched in metastatic niche to promote growth of BCBMs. Herein, it is reported that nanoparticles (NPs-K-s-A) tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2 (A), can surmount the BBB and escape LRP1-mediated clearance in metastatic niche. NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice, while comparable brain accumulation in normal mice. The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs. Due to the efficient BBB penetration, special and remarkable clearance escape, and facilitated therapeutic outcome, the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs.

Indexed as

231Br, MDA-MB-231Br-HER2A, angiopep-2Abluminal LRP1Amyloid betaAUC0‒t, area under the curve from zero to time tAβ, amyloid betaBBB, blood‒brain barrierBCBMs, breast cancer brain metastasesBlood‒brain barrierBMECs, brain microvascular endothelial cellsBrain clearanceBreast cancer brain metastasesCI, combination indexCL, clearanceDMEM, Dulbecco's modified eagle mediumDMSO, dimethyl sulfoxideDOX, doxorubicinFa, the fraction of tumor cells affectedFBS, fetal bovine serumFusion peptidei, insensitive GDQGIAGFK, KAAYSLLAP, lapatinibLRP1, low density lipoprotein receptor-related protein 1MAL-PEG-SCM, maleimide polyethylene glycol succinimidyl carboxymethyl esterMCM, MDA-MB-231Br-HER2 conditioned mediumMMPMMP1, matrix metalloproteinase-1MRT0‒t, mean residence time from zero to time tNanoparticlesNPs, nanoparticlesPLGA-PLL, poly(lactic-co-glycolic acid)-poly(ε-carbobenzoxy-l-lysine)PLGA, poly(lactic-co-glycolic acid)PLL, poly(ε-carbobenzoxy-l-lysine)PVA, polyvinyl alcoholSDS, sodium dodecyl sulfates, sensitive VPMS-MRGGt1/2, half timetPA, tissue plasminogen activator

Identifiers

PMID34094838
PMCPMC8148067
OpenAlexW3094107482

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.