Cited by 124RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryImmune cells in cancer

Tumor associated macrophage-targeted microRNA delivery with dual-responsive polypeptide nanovectors for anti-cancer therapy

Liu, Lanlan, Yi, Huqiang, He, Huamei, Pan, Hong, Cai, Lintao, Ma, Yifan·2017·Biomaterials

Abstract

Repolarizing Tumor-associated macrophages (TAMs) to anti-tumor M1 macrophages with microRNA (miR) is a plausible approach for cancer treatment. However, how to achieve TAM-targeted miR delivery remains a challenge. The present study generated redox/pH dual-responsive hybrid polypeptide nanovectors, which consisted of self-crosslinked redox-responsive nanoparticles based on galactose-functionalized n-butylamine-poly(l-lysine)-b-poly(l-cysteine) polypeptides (GLC) coated with DCA-grafted sheddable PEG-PLL (sPEG) copolymers. The ex vivo study showed that sPEG shielded cationic GLC core at physiological pH but quickly shed off to re-expose GLC due to it charge reversible property. Encapsulation with sPEG/GLC nanovectors effectively facilitated macrophage-targeted miR delivery at the acidic condition but diminished miR uptake at neutral pH. Administration of miR155-loaded sPEG/GLC (sPEG/GLC/155) nanocomplexes increased miR155 expression in TAMs about 100-400 folds both in vitro and in vivo. sPEG/GLC/155 also effectively repolarized immunosuppressive TAMs to anti-tumor M1 macrophages through elevating M1 macrophage markers (IL-12, iNOS, MHC II) and suppressing M2 macrophage markers (Msr2 and Arg1) in TAMs. Moreover, the treatment of sPEG/GLC/155 significantly increased activated T lymphocytes and NK cells in tumors, which consequently led to robust tumor regression. Hence, TAM-targeted delivery of miR with redox/pH dual-responsive sPEG/GLC nanovectors could be a promising approach to re-polarize TAMs to M1 macrophages in situ and induce tumor regression.

Integrity signals

Registry

Crossref · 10.1016/j.biomaterials.2017.04.043

Cites

46 of 46 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Extensive efforts on facilitating particle accumulation in targeted tissues for non-viral delivery vectors-mediated gene therapy exist.

    “In the past decades, there have been extensive efforts on facilitating particles accumulation in the targeted tissues for non-viral delivery vectors-mediated gene therapy [155, 156].”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Liu, L., Yi, H., He, H., Pan, H., Cai, L., & Ma, Y.
Affiliations
Chinese Academy of Sciences (CN)
Corresponding author
  • Cai, Lintao
  • Ma, Yifan
Venue
Biomaterials
Publisher
Elsevier BV
Published
2017-07
Volume
134
Pages
166-179
ISSN
0142-9612 (ISSN-L)
OpenAlex
W2608151576
Cited by
124
References
46
Citations by year
2026: 4 · 2025: 6 · 2024: 10 · 2023: 9 · 2022: 14 · 2021: 30 · 2020: 18 · 2019: 16 · 2018: 16 · 2017: 1
FWCI
5.69
Type
journal article
Language
en
Open access
closed
Locations
  • Biomaterials (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81371679, 31571013, 21375141, 81401509, 81501580)
  • Key International S&T Cooperation Project (2015DFH50230)
  • Instrument Developing Project of CAS (YZ201439)
  • Guangdong Natural Science Foundation of Research Team (2016A030312006)
  • Shenzhen Science and Technology Program (KQCX20140521115045447, JCYJ20150401145529015, JCYJ20130402092657771, JSGG20160331185422390, JCYJ20150521094519473, JCYJ20160429191503002)
  • SIAT Innovation Program for Excellent Young Researchers (201506)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords
tumor-associated macrophages, macrophage repolarization, M1 macrophages, microRNA delivery, miR-155, redox-responsive nanoparticles, pH-responsive nanoparticles, dual-responsive drug delivery, cancer immunotherapy, tumor regression
MeSH terms
RAW 264.7 Cells, Animals, Electrophoresis, Agar Gel, Female, Killer Cells, Natural, Melanoma, Melanoma, Experimental, Mice, Inbred C57BL, Mice, Nude, Magnetic Resonance Spectroscopy, Peptides, T-Lymphocytes, Signal Transduction, Interleukin-12, MicroRNAs, Mice, Nitric Oxide Synthase Type II, Nanoparticles

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review