Evidence map›Paper›PMID 30817164›Full record

ArticleMolecular pharmaceutics2019

Selective Cytotoxicity to HER2 Positive Breast Cancer Cells by Saporin-Loaded Nanobody-Targeted Polymeric Nanoparticles in Combination with Photochemical Internalization.

Lucía Martínez-Jothar, Nataliia Beztsinna, Cornelus F van Nostrum, Wim E Hennink, Sabrina Oliveira

Abstract read
In one paragraph

Article in Molecular pharmaceutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing 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.

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

29 citing papers in PubMed.

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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

5 authors.

Lucía Martínez-JotharDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences , Utrecht University , Universiteitsweg 99 , 3584 CG Utrecht , The Netherlands.
Nataliia BeztsinnaDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences , Utrecht University , Universiteitsweg 99 , 3584 CG Utrecht , The Netherlands.
Cornelus F van NostrumDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences , Utrecht University , Universiteitsweg 99 , 3584 CG Utrecht , The Netherlands.ORCID 0000-0003-4210-5241
Wim E HenninkDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences , Utrecht University , Universiteitsweg 99 , 3584 CG Utrecht , The Netherlands.ORCID 0000-0002-5750-714X
Sabrina OliveiraDepartment of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences , Utrecht University , Universiteitsweg 99 , 3584 CG Utrecht , The Netherlands.ORCID 0000-0002-6011-2122

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In cancer treatment, polymeric nanoparticles (NPs) can serve as a vehicle for the delivery of cytotoxic proteins that have intracellular targets but that lack well-defined mechanisms for cellular internalization, such as saporin. In this work, we have prepared PEGylated poly(lactic acid- co-glycolic acid- co-hydroxymethyl glycolic acid) (PLGHMGA) NPs for the selective delivery of saporin in the cytosol of HER2 positive cancer cells. This selective uptake was achieved by decorating the surface of the NPs with the 11A4 nanobody that is specific for the HER2 receptor. Confocal microscopy observations showed rapid and extensive uptake of the targeted NPs (11A4-NPs) by HER2 positive cells (SkBr3) but not by HER2 negative cells (MDA-MB-231). This selective uptake was blocked upon preincubation of the cells with an excess of nanobody. Nontargeted NPs (Cys-NPs) were not taken up by either type of cells. Importantly, a dose-dependent cytotoxic effect was only observed on SkBr3 cells when these were treated with saporin-loaded 11A4-NPs in combination with photochemical internalization (PCI), a technique that uses a photosensitizer and local light exposure to facilitate endosomal escape of entrapped nanocarriers and biomolecules. The combined use of saporin-loaded 11A4-NPs and PCI strongly inhibited cell proliferation and decreased cell viability through induction of apoptosis. Also the cytotoxic effect could be reduced by an excess of nanobody, reinforcing the selectivity of this system. These results suggest that the combination of the targeting nanobody on the NPs with PCI are effective means to achieve selective uptake and cytotoxicity of saporin-loaded NPs.

Indexed as

Antineoplastic AgentsApoptosisBreast NeoplasmsCell ProliferationDrug CarriersDrug Delivery SystemsErb-b2 Receptor Tyrosine KinasesFemaleHumansNanoparticlesPhotochemotherapyPhotosensitizing AgentsPolyestersPolymersSaporinsSingle-Domain AntibodiesAntineoplastic AgentsDrug CarriersERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesPhotosensitizing AgentsPolyesterspoly(lactic-co-glycolic-co-hydroxymethylglycolic acid)PolymersSaporinsSingle-Domain Antibodiesnanobodyphotochemical internalizationPLGApolymeric nanoparticlessaporintargeting

Identifiers

PMID30817164
PMCPMC6448105

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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.