Self-Assembled Silk Fibroin-Based Aggregates for Delivery of Camptothecin

A water-soluble hydrolysate of silk fibroin (SF) (~30 kDa) was esterified with tocopherol, ergocalciferol, and testosterone to form SF aggregates for the controlled delivery of the anticancer drug camptothecin (CPT). Elemental analysis and <sup>1</sup>H NMR spectroscopy showed a degree o...

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Autores principales:	Javier Pérez Quiñones, Cornelia Roschger, Andreas Zierer, Carlos Peniche-Covas, Oliver Brüggemann
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	silk fibroin camptothecin controlled release nanoaggregates antitumor activity Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/778cbf6206614bc1ae7baa0349283737
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spelling	oai:doaj.org-article:778cbf6206614bc1ae7baa03492837372021-11-11T18:47:49ZSelf-Assembled Silk Fibroin-Based Aggregates for Delivery of Camptothecin10.3390/polym132138042073-4360https://doaj.org/article/778cbf6206614bc1ae7baa03492837372021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4360/13/21/3804https://doaj.org/toc/2073-4360A water-soluble hydrolysate of silk fibroin (SF) (~30 kDa) was esterified with tocopherol, ergocalciferol, and testosterone to form SF aggregates for the controlled delivery of the anticancer drug camptothecin (CPT). Elemental analysis and <sup>1</sup>H NMR spectroscopy showed a degree of substitution (DS) on SF of 0.4 to 3.8 mol %. Yields of 58 to 71% on vitamins- and testosterone-grafted SF conjugates were achieved. CPT was efficiently incorporated into the lipophilic core of SF aggregates using a dialysis–precipitation method, achieving drug contents of 6.3–8.5 wt %. FTIR spectra and DSC thermograms showed that tocopherol- and testosterone-grafted SF conjugates predominantly adopted a β-sheet conformation. After the esterification of tyrosine residues on SF chains with the vitamin or testosterone, the hydrodynamic diameters almost doubled or tripled that of SF. The zeta potential values after esterification increased to about −30 mV, which favors the stability of aggregates in aqueous medium. Controlled and almost quantitative release of CPT was achieved after 6 days in PBS at 37 °C, with almost linear release during the first 8 h. MCF-7 cancer cells exhibited good uptake of CPT-loaded SF aggregates after 6 h, causing cell death and cell cycle arrest in the G2/M phase. Substantial uptake of the CPT-loaded aggregates into MCF-7 spheroids was shown after 3 days. Furthermore, all CPT-loaded SF aggregates demonstrated superior toxicity to MCF-7 spheroids compared with parent CPT. Blank SF aggregates induced no hemolysis at pH 6.2 and 7.4, while CPT-loaded SF aggregates provoked hemolysis at pH 6.2 but not at pH 7.4. In contrast, parent CPT caused hemolysis at both pH tested. Therefore, CPT-loaded SF aggregates are promising candidates for chemotherapy.Javier Pérez QuiñonesCornelia RoschgerAndreas ZiererCarlos Peniche-CovasOliver BrüggemannMDPI AGarticlesilk fibroincamptothecincontrolled releasenanoaggregatesantitumor activityOrganic chemistryQD241-441ENPolymers, Vol 13, Iss 3804, p 3804 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	silk fibroin camptothecin controlled release nanoaggregates antitumor activity Organic chemistry QD241-441
spellingShingle	silk fibroin camptothecin controlled release nanoaggregates antitumor activity Organic chemistry QD241-441 Javier Pérez Quiñones Cornelia Roschger Andreas Zierer Carlos Peniche-Covas Oliver Brüggemann Self-Assembled Silk Fibroin-Based Aggregates for Delivery of Camptothecin
description	A water-soluble hydrolysate of silk fibroin (SF) (~30 kDa) was esterified with tocopherol, ergocalciferol, and testosterone to form SF aggregates for the controlled delivery of the anticancer drug camptothecin (CPT). Elemental analysis and <sup>1</sup>H NMR spectroscopy showed a degree of substitution (DS) on SF of 0.4 to 3.8 mol %. Yields of 58 to 71% on vitamins- and testosterone-grafted SF conjugates were achieved. CPT was efficiently incorporated into the lipophilic core of SF aggregates using a dialysis–precipitation method, achieving drug contents of 6.3–8.5 wt %. FTIR spectra and DSC thermograms showed that tocopherol- and testosterone-grafted SF conjugates predominantly adopted a β-sheet conformation. After the esterification of tyrosine residues on SF chains with the vitamin or testosterone, the hydrodynamic diameters almost doubled or tripled that of SF. The zeta potential values after esterification increased to about −30 mV, which favors the stability of aggregates in aqueous medium. Controlled and almost quantitative release of CPT was achieved after 6 days in PBS at 37 °C, with almost linear release during the first 8 h. MCF-7 cancer cells exhibited good uptake of CPT-loaded SF aggregates after 6 h, causing cell death and cell cycle arrest in the G2/M phase. Substantial uptake of the CPT-loaded aggregates into MCF-7 spheroids was shown after 3 days. Furthermore, all CPT-loaded SF aggregates demonstrated superior toxicity to MCF-7 spheroids compared with parent CPT. Blank SF aggregates induced no hemolysis at pH 6.2 and 7.4, while CPT-loaded SF aggregates provoked hemolysis at pH 6.2 but not at pH 7.4. In contrast, parent CPT caused hemolysis at both pH tested. Therefore, CPT-loaded SF aggregates are promising candidates for chemotherapy.
format	article
author	Javier Pérez Quiñones Cornelia Roschger Andreas Zierer Carlos Peniche-Covas Oliver Brüggemann
author_facet	Javier Pérez Quiñones Cornelia Roschger Andreas Zierer Carlos Peniche-Covas Oliver Brüggemann
author_sort	Javier Pérez Quiñones
title	Self-Assembled Silk Fibroin-Based Aggregates for Delivery of Camptothecin
title_short	Self-Assembled Silk Fibroin-Based Aggregates for Delivery of Camptothecin
title_full	Self-Assembled Silk Fibroin-Based Aggregates for Delivery of Camptothecin
title_fullStr	Self-Assembled Silk Fibroin-Based Aggregates for Delivery of Camptothecin
title_full_unstemmed	Self-Assembled Silk Fibroin-Based Aggregates for Delivery of Camptothecin
title_sort	self-assembled silk fibroin-based aggregates for delivery of camptothecin
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/778cbf6206614bc1ae7baa0349283737
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Self-Assembled Silk Fibroin-Based Aggregates for Delivery of Camptothecin

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