Targeted Prodrug-Based Self-Assembled Nanoparticles for Cancer Therapy.
Animals
Antineoplastic Agents, Phytogenic
/ administration & dosage
Apoptosis
/ drug effects
Cell Line, Tumor
Drug Delivery Systems
/ methods
Female
Fluorescein-5-isothiocyanate
/ chemistry
Glucosamine
/ chemistry
Glutamic Acid
/ chemistry
Humans
Mice, Inbred BALB C
Nanoparticles
/ administration & dosage
Paclitaxel
/ administration & dosage
Prodrugs
/ chemistry
Xenograft Model Antitumor Assays
NIR imaging
chemotherapy
nanoplatform
targeted prodrug
Journal
International journal of nanomedicine
ISSN: 1178-2013
Titre abrégé: Int J Nanomedicine
Pays: New Zealand
ID NLM: 101263847
Informations de publication
Date de publication:
2020
2020
Historique:
received:
29
01
2020
accepted:
07
04
2020
entrez:
20
5
2020
pubmed:
20
5
2020
medline:
14
7
2020
Statut:
epublish
Résumé
Targeted prodrug has various applications as drug formulation for tumor therapy. Therefore, amphoteric small-molecule prodrug combined with nanoscale characteristics for the self-assembly of the nano-drug delivery system (DDS) is a highly interesting research topic. In this study, we developed a prodrug self-assembled nanoplatform, 2-glucosamine-fluorescein-5(6)-isothiocyanate-glutamic acid-paclitaxel (2DA-FITC-PTX NPs) by integration of targeted small molecule and nano-DDS with regular structure and perfect targeting ability. 2-glucosamine (DA) and paclitaxel were conjugated as the targeted ligand and anti-tumor chemotherapy drug by amino acid group. 2-DA molecular structure can enhance the targeting ability of prodrug-based 2DA-FITC-PTX NPs and prolong retention time, thereby reducing the toxicity of normal cell/tissue. The fluorescent dye FITC or near-infrared fluorescent dye ICG in prodrug-based DDS was attractive for in vivo optical imaging to study the behavior of 2DA-FITC-PTX NPs. In vitro and in vivo results proved that 2DA-FITC-PTX NPs exhibited excellent targeting ability, anticancer activity, and weak side effects. This work demonstrates a new combination of nanomaterials for chemotherapy and may promote prodrug-based DDS clinical applications in the future.
Sections du résumé
BACKGROUND
BACKGROUND
Targeted prodrug has various applications as drug formulation for tumor therapy. Therefore, amphoteric small-molecule prodrug combined with nanoscale characteristics for the self-assembly of the nano-drug delivery system (DDS) is a highly interesting research topic.
METHODS AND RESULTS
RESULTS
In this study, we developed a prodrug self-assembled nanoplatform, 2-glucosamine-fluorescein-5(6)-isothiocyanate-glutamic acid-paclitaxel (2DA-FITC-PTX NPs) by integration of targeted small molecule and nano-DDS with regular structure and perfect targeting ability. 2-glucosamine (DA) and paclitaxel were conjugated as the targeted ligand and anti-tumor chemotherapy drug by amino acid group. 2-DA molecular structure can enhance the targeting ability of prodrug-based 2DA-FITC-PTX NPs and prolong retention time, thereby reducing the toxicity of normal cell/tissue. The fluorescent dye FITC or near-infrared fluorescent dye ICG in prodrug-based DDS was attractive for in vivo optical imaging to study the behavior of 2DA-FITC-PTX NPs. In vitro and in vivo results proved that 2DA-FITC-PTX NPs exhibited excellent targeting ability, anticancer activity, and weak side effects.
CONCLUSION
CONCLUSIONS
This work demonstrates a new combination of nanomaterials for chemotherapy and may promote prodrug-based DDS clinical applications in the future.
Identifiants
pubmed: 32425524
doi: 10.2147/IJN.S247443
pii: 247443
pmc: PMC7187935
doi:
Substances chimiques
Antineoplastic Agents, Phytogenic
0
Prodrugs
0
Glutamic Acid
3KX376GY7L
Fluorescein-5-isothiocyanate
I223NX31W9
Glucosamine
N08U5BOQ1K
Paclitaxel
P88XT4IS4D
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2921-2933Informations de copyright
© 2020 Wang et al.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
Références
Theranostics. 2018 Feb 16;8(7):2018-2030
pubmed: 29556370
Bioconjug Chem. 2018 Dec 19;29(12):3967-3981
pubmed: 30485070
Biomaterials. 2016 Apr;85:152-67
pubmed: 26871891
Nat Rev Cancer. 2017 Jan;17(1):20-37
pubmed: 27834398
Exp Oncol. 2019 Mar;41(1):14-19
pubmed: 30932416
Biomaterials. 2012 Jan;33(1):146-62
pubmed: 21959006
Eur J Pharm Biopharm. 2015 Nov;97(Pt B):454-63
pubmed: 26614563
FASEB J. 2018 Sep;32(9):5104-5118
pubmed: 29913554
J Drug Target. 2016;24(1):68-79
pubmed: 26152812
Bioconjug Chem. 2010 Apr 21;21(4):604-9
pubmed: 20369817
Int J Cancer. 2003 Nov 1;107(2):177-82
pubmed: 12949791
Curr Med Chem. 2019;26(14):2410-2429
pubmed: 28699504
Cell Rep. 2020 Jan 14;30(2):481-496.e6
pubmed: 31940491
Med Chem. 2018;14(4):322-332
pubmed: 29332599
Apoptosis. 2018 Jun;23(5-6):290-298
pubmed: 29663099
Angew Chem Int Ed Engl. 2019 Apr 23;58(18):5920-5924
pubmed: 30793456
Int J Nanomedicine. 2015 Sep 01;10:5571-91
pubmed: 26366078
Mol Biol Cell. 2014 Sep 15;25(18):2677-81
pubmed: 25213191
ACS Nano. 2019 Aug 27;13(8):9386-9396
pubmed: 31375027
Nano Lett. 2014 Jul 9;14(7):3697-701
pubmed: 24884872
J Am Chem Soc. 2014 Aug 20;136(33):11748-56
pubmed: 25078892
ACS Nano. 2019 Aug 27;13(8):8903-8916
pubmed: 31374171
Chem Commun (Camb). 2019 Dec 28;55(100):15057-15060
pubmed: 31777882
Adv Drug Deliv Rev. 2017 Feb;110-111:112-126
pubmed: 27370248
Bioconjug Chem. 2016 Nov 16;27(11):2722-2733
pubmed: 27723981
Regul Toxicol Pharmacol. 2018 Oct;98:184-189
pubmed: 30075180
Molecules. 2019 Jun 07;24(11):
pubmed: 31181707
Int J Pharm. 2020 Feb 15;575:118980
pubmed: 31899320
Bioorg Med Chem Lett. 2018 Feb 15;28(4):826-830
pubmed: 29395972
Drug Deliv. 2018 Nov;25(1):153-165
pubmed: 29282992
Drug Discov Today. 2017 Nov;22(11):1637-1653
pubmed: 28843632
Adv Mater. 2017 Sep;29(36):
pubmed: 28714209
Mater Sci Eng C Mater Biol Appl. 2019 May;98:1252-1276
pubmed: 30813007
Cold Spring Harb Protoc. 2016 Mar 01;2016(3):pdb.prot087395
pubmed: 26933245
Adv Drug Deliv Rev. 2017 Sep 1;118:65-77
pubmed: 28676386
Pharmazie. 2012 Sep;67(9):756-64
pubmed: 23016447
Int J Pharm. 2018 May 30;543(1-2):368-375
pubmed: 29630933
J Drug Target. 2016 Sep;24(8):730-43
pubmed: 26878084
Adv Drug Deliv Rev. 2013 Jan;65(1):71-9
pubmed: 23088862
Mol Pharm. 2019 Sep 3;16(9):3770-3779
pubmed: 31348660
J Control Release. 2017 Oct 28;264:145-159
pubmed: 28844757
Biomaterials. 2020 Feb;232:119701
pubmed: 31901505
Biomed Pharmacother. 2017 Oct;94:402-411
pubmed: 28772219
Chem Soc Rev. 2018 Jan 2;47(1):28-52
pubmed: 29057403