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Functionalized Folic Acid-Conjugated Amphiphilic Alternating Copolymer Actively Targets 3D Multicellular Tumour Spheroids and Delivers the Hydrophobic Drug to the Inner Core

Engineering of a “smart” drug delivery system to specifically target tumour cells has been at the forefront of cancer research, having been engineered for safer, more efficient and effective use of chemotherapy for the treatment of cancer. However, selective targeting and choosing the right cancer s...

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Autores principales: Li, Xia, Sambi, Manpreet, DeCarlo, Alexandria, Burov, Sergey V., Akasov, Roman, Markvicheva, Elena, Malardier-Jugroot, Cecile, Szewczuk, Myron R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116205/
https://www.ncbi.nlm.nih.gov/pubmed/30072655
http://dx.doi.org/10.3390/nano8080588
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author Li, Xia
Sambi, Manpreet
DeCarlo, Alexandria
Burov, Sergey V.
Akasov, Roman
Markvicheva, Elena
Malardier-Jugroot, Cecile
Szewczuk, Myron R.
author_facet Li, Xia
Sambi, Manpreet
DeCarlo, Alexandria
Burov, Sergey V.
Akasov, Roman
Markvicheva, Elena
Malardier-Jugroot, Cecile
Szewczuk, Myron R.
author_sort Li, Xia
collection PubMed
description Engineering of a “smart” drug delivery system to specifically target tumour cells has been at the forefront of cancer research, having been engineered for safer, more efficient and effective use of chemotherapy for the treatment of cancer. However, selective targeting and choosing the right cancer surface biomarker are critical for a targeted treatment to work. Currently, the available delivery systems use a two-dimensional monolayer of cancer cells to test the efficacy of the drug delivery system, but designing a “smart” drug delivery system to be specific for a tumour in vivo and to penetrate the inner core remains a major design challenge. These challenges can be overcome by using a study model that integrates the three-dimensional aspect of a tumour in a culture system. Here, we tested the efficacy of a functionalized folic acid-conjugated amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA) to specifically target and penetrate the inner core of three-dimensional avascular human pancreatic and breast tumour spheroids in culture. The copolymer was quantitatively analyzed for its hydrophobic drug encapsulation efficiency using three different chemical drug structures with different molecular weights. Their release profiles and tumour targeting properties at various concentrations and pH environments were also characterized. Using the anticancer drug curcumin and two standard clinical chemotherapeutic hydrophobic drugs, paclitaxel and 5-fluorouracil, we tested the ability of FA-DABA-SMA nanoparticles to encapsulate the differently sized drugs and deliver them to kill monolayer pancreatic cancer cells using the WST-1 cell proliferation assay. The findings of this study revealed that the functionalized folic acid-conjugated amphiphilic alternating copolymer shows unique properties as an active “smart” tumor-targeting drug delivery system with the ability to internalize hydrophobic drugs and release the chemotherapeutics for effective killing of cancer cells. The novelty of the study is the first to demonstrate a functionalized “smart” drug delivery system encapsulated with a hydrophobic drug effectively targeting and penetrating the inner core of pancreatic and breast cancer spheroids and reducing their volumes in a dose- and time-dependent manner.
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spelling pubmed-61162052018-08-31 Functionalized Folic Acid-Conjugated Amphiphilic Alternating Copolymer Actively Targets 3D Multicellular Tumour Spheroids and Delivers the Hydrophobic Drug to the Inner Core Li, Xia Sambi, Manpreet DeCarlo, Alexandria Burov, Sergey V. Akasov, Roman Markvicheva, Elena Malardier-Jugroot, Cecile Szewczuk, Myron R. Nanomaterials (Basel) Article Engineering of a “smart” drug delivery system to specifically target tumour cells has been at the forefront of cancer research, having been engineered for safer, more efficient and effective use of chemotherapy for the treatment of cancer. However, selective targeting and choosing the right cancer surface biomarker are critical for a targeted treatment to work. Currently, the available delivery systems use a two-dimensional monolayer of cancer cells to test the efficacy of the drug delivery system, but designing a “smart” drug delivery system to be specific for a tumour in vivo and to penetrate the inner core remains a major design challenge. These challenges can be overcome by using a study model that integrates the three-dimensional aspect of a tumour in a culture system. Here, we tested the efficacy of a functionalized folic acid-conjugated amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA) to specifically target and penetrate the inner core of three-dimensional avascular human pancreatic and breast tumour spheroids in culture. The copolymer was quantitatively analyzed for its hydrophobic drug encapsulation efficiency using three different chemical drug structures with different molecular weights. Their release profiles and tumour targeting properties at various concentrations and pH environments were also characterized. Using the anticancer drug curcumin and two standard clinical chemotherapeutic hydrophobic drugs, paclitaxel and 5-fluorouracil, we tested the ability of FA-DABA-SMA nanoparticles to encapsulate the differently sized drugs and deliver them to kill monolayer pancreatic cancer cells using the WST-1 cell proliferation assay. The findings of this study revealed that the functionalized folic acid-conjugated amphiphilic alternating copolymer shows unique properties as an active “smart” tumor-targeting drug delivery system with the ability to internalize hydrophobic drugs and release the chemotherapeutics for effective killing of cancer cells. The novelty of the study is the first to demonstrate a functionalized “smart” drug delivery system encapsulated with a hydrophobic drug effectively targeting and penetrating the inner core of pancreatic and breast cancer spheroids and reducing their volumes in a dose- and time-dependent manner. MDPI 2018-08-02 /pmc/articles/PMC6116205/ /pubmed/30072655 http://dx.doi.org/10.3390/nano8080588 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Li, Xia
Sambi, Manpreet
DeCarlo, Alexandria
Burov, Sergey V.
Akasov, Roman
Markvicheva, Elena
Malardier-Jugroot, Cecile
Szewczuk, Myron R.
Functionalized Folic Acid-Conjugated Amphiphilic Alternating Copolymer Actively Targets 3D Multicellular Tumour Spheroids and Delivers the Hydrophobic Drug to the Inner Core
title Functionalized Folic Acid-Conjugated Amphiphilic Alternating Copolymer Actively Targets 3D Multicellular Tumour Spheroids and Delivers the Hydrophobic Drug to the Inner Core
title_full Functionalized Folic Acid-Conjugated Amphiphilic Alternating Copolymer Actively Targets 3D Multicellular Tumour Spheroids and Delivers the Hydrophobic Drug to the Inner Core
title_fullStr Functionalized Folic Acid-Conjugated Amphiphilic Alternating Copolymer Actively Targets 3D Multicellular Tumour Spheroids and Delivers the Hydrophobic Drug to the Inner Core
title_full_unstemmed Functionalized Folic Acid-Conjugated Amphiphilic Alternating Copolymer Actively Targets 3D Multicellular Tumour Spheroids and Delivers the Hydrophobic Drug to the Inner Core
title_short Functionalized Folic Acid-Conjugated Amphiphilic Alternating Copolymer Actively Targets 3D Multicellular Tumour Spheroids and Delivers the Hydrophobic Drug to the Inner Core
title_sort functionalized folic acid-conjugated amphiphilic alternating copolymer actively targets 3d multicellular tumour spheroids and delivers the hydrophobic drug to the inner core
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6116205/
https://www.ncbi.nlm.nih.gov/pubmed/30072655
http://dx.doi.org/10.3390/nano8080588
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