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Lipoproteins LDL versus HDL as nanocarriers to target either cancer cells or macrophages
- Source :
- JCI Insight, JCI Insight, American Society for Clinical Investigation, In press, pp.140280. ⟨10.1172/jci.insight.140280⟩, JCI Insight, Vol 5, Iss 24 (2020), JCI Insight, 2020, 5 (24), pp.e140280. ⟨10.1172/jci.insight.140280⟩, JCI Insight, American Society for Clinical Investigation, 2020, 5 (24), pp.e140280. ⟨10.1172/jci.insight.140280⟩
- Publication Year :
- 2020
- Publisher :
- HAL CCSD, 2020.
-
Abstract
- free open access article 31 p.; International audience; In this work, we have explored natural unmodified low- and high-density lipoproteins (LDL and HDL) as selective delivery vectors in colorectal cancer therapy. We show in vitro in cultured cells and in vivo (NanoSPECT/CT) in the CT-26 mice colorectal cancer model that LDLs are mainly taken up by cancer cells, while HDLs are preferentially taken up by macrophages. We loaded LDLs with cisplatin and HDLs with the heat shock protein-70 inhibitor AC1LINNC, turning them into a pair of “Trojan horses” delivering drugs selectively to their target cells as demonstrated in vitro in human colorectal cancer cells and macrophages, and in vivo. Coupling of the drugs to lipoproteins and stability was assessed by mass and raman spectrometry analysis. Cisplatin vectorized in LDLs led to better tumor growth suppression with strongly reduced adverse effects such as a renal or liver toxicity. AC1LINNC vectorized into HDLs induced a strong oxidative burst in macrophages and innate anti-cancer immune response. Cumulative anti-tumor effect was observed for both drug-loaded lipoproteins. Altogether, our data show that lipoproteins from patient’s blood can be used as natural nanocarriers allowing cell specific targeting, paving the way toward more efficient, safer and personalized use of chemo-and immunotherapeutic drugs in cancer
- Subjects :
- 0301 basic medicine
medicine.medical_treatment
cisplatin
lcsh:Medicine
heat shock protein inhibitor
Cancer immunotherapy
[CHIM.THER]Chemical Sciences/Medicinal Chemistry
Spectrum Analysis, Raman
Mice
Drug Delivery Systems
0302 clinical medicine
Chemistry
selective cell targeting
General Medicine
3. Good health
Lipoproteins, LDL
Oncology
030220 oncology & carcinogenesis
Medicine
cancer therapy
lipids (amino acids, peptides, and proteins)
Colorectal Neoplasms
Lipoproteins, HDL
Research Article
medicine.drug
[CHIM.THER] Chemical Sciences/Medicinal Chemistry
Lipoproteins
Therapeutics
Cell Line
03 medical and health sciences
Immune system
In vivo
Cell Line, Tumor
medicine
vectorization
Animals
Humans
Cisplatin
Macrophages
lcsh:R
Cancer
medicine.disease
Colorectal cancer
In vitro
030104 developmental biology
Cancer cell
Cancer research
Nanocarriers
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Subjects
Details
- Language :
- English
- ISSN :
- 23793708
- Database :
- OpenAIRE
- Journal :
- JCI Insight, JCI Insight, American Society for Clinical Investigation, In press, pp.140280. ⟨10.1172/jci.insight.140280⟩, JCI Insight, Vol 5, Iss 24 (2020), JCI Insight, 2020, 5 (24), pp.e140280. ⟨10.1172/jci.insight.140280⟩, JCI Insight, American Society for Clinical Investigation, 2020, 5 (24), pp.e140280. ⟨10.1172/jci.insight.140280⟩
- Accession number :
- edsair.doi.dedup.....f4c0e61726aced7e413c2e9559b2eaa5