Development of Surface Chemical Strategies for Synthesizing Redox-Responsive Diatomite Nanoparticles as a Green Platform for On-Demand Intracellular Release of an Antisense Peptide Nucleic Acid Anticancer Agent

Monica Terracciano; Flavia Fontana; Andrea Patrizia Falanga; Stefano D'Errico; Giulia Torrieri; Francesca Greco; Chiara Tramontano; Ilaria Rea; Gennaro Piccialli; Luca De Stefano; Giorgia Oliviero; Hélder A. Santos; Nicola Borbone

doi:10.1002/smll.202204732

Development of Surface Chemical Strategies for Synthesizing Redox-Responsive Diatomite Nanoparticles as a Green Platform for On-Demand Intracellular Release of an Antisense Peptide Nucleic Acid Anticancer Agent

Monica Terracciano, Flavia Fontana, Andrea Patrizia Falanga, Stefano D'Errico, Giulia Torrieri, Francesca Greco, Chiara Tramontano, Ilaria Rea, Gennaro Piccialli, Luca De Stefano, Giorgia Oliviero, Hélder A. Santos^*, Nicola Borbone^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

12 Citations (Scopus)

108 Downloads (Pure)

Abstract

Abstract Redox-responsive silica drug delivery systems are synthesized by aeco-friendly diatomite source to achieve on-demand release of peptide nucleic acid (PNA) in tumor reducing microenvironment, aiming to inhibit the immune checkpoint programmed cell death 1 receptor/programmed cell death receptor ligand 1 (PD-1/PD-L1) in cancer cells. The nanoparticles (NPs) are coated with polyethylene glycol chains as gatekeepers to improve their physicochemical properties and control drug release through the cleavable disulfide bonds (S?S) in a reductive environment. This study describes different chemical conditions to achieve the highest NPs? surface functionalization yield, exploring both multistep and one-pot chemical functionalization strategies. The best formulation is used for covalent PNA conjugation via the S?S bond reaching a loading degree of 306 ± 25 µg PNA mg?1DNPs. These systems are used for in vitro studies to evaluate the kinetic release, biocompatibility, cellular uptake, and activity on different cancer cells expressing high levels of PD-L1. The obtained results prove the safety of the NPs up to 200 µg mL?1 and their advantage for controlling and enhancing the PNA intracellular release as well as antitumor activity. Moreover, the downregulation of PD-L1 observed only with MDA-MB-231 cancer cells paves the way for targeted immunotherapy.

Original language	English
Article number	2204732
Number of pages	14
Journal	Small
Volume	18
Issue number	41
DOIs	https://doi.org/10.1002/smll.202204732
Publication status	Published - 11-Sept-2022

Keywords

diatomite nanoparticles
gene therapy
peptide nucleic acids
redox-responsive
surface chemistry

Access to Document

10.1002/smll.202204732Licence: CC BY

Small - 2022 - Terracciano - Development of Surface Chemical Strategies for Synthesizing Redox‐Responsive DiatomiteFinal publisher's version, 6.07 MBLicence: CC BY

Handle.net

Persistent link

Fingerprint

Dive into the research topics of 'Development of Surface Chemical Strategies for Synthesizing Redox-Responsive Diatomite Nanoparticles as a Green Platform for On-Demand Intracellular Release of an Antisense Peptide Nucleic Acid Anticancer Agent'. Together they form a unique fingerprint.

Cite this

Terracciano, M., Fontana, F., Falanga, A. P., D'Errico, S., Torrieri, G., Greco, F., Tramontano, C., Rea, I., Piccialli, G., De Stefano, L., Oliviero, G., Santos, H. A., & Borbone, N. (2022). Development of Surface Chemical Strategies for Synthesizing Redox-Responsive Diatomite Nanoparticles as a Green Platform for On-Demand Intracellular Release of an Antisense Peptide Nucleic Acid Anticancer Agent. Small, 18(41), Article 2204732. https://doi.org/10.1002/smll.202204732

@article{9f60b8ac1a924ea88d8762f1195d968d,

title = "Development of Surface Chemical Strategies for Synthesizing Redox-Responsive Diatomite Nanoparticles as a Green Platform for On-Demand Intracellular Release of an Antisense Peptide Nucleic Acid Anticancer Agent",

abstract = "Abstract Redox-responsive silica drug delivery systems are synthesized by aeco-friendly diatomite source to achieve on-demand release of peptide nucleic acid (PNA) in tumor reducing microenvironment, aiming to inhibit the immune checkpoint programmed cell death 1 receptor/programmed cell death receptor ligand 1 (PD-1/PD-L1) in cancer cells. The nanoparticles (NPs) are coated with polyethylene glycol chains as gatekeepers to improve their physicochemical properties and control drug release through the cleavable disulfide bonds (S?S) in a reductive environment. This study describes different chemical conditions to achieve the highest NPs? surface functionalization yield, exploring both multistep and one-pot chemical functionalization strategies. The best formulation is used for covalent PNA conjugation via the S?S bond reaching a loading degree of 306 ± 25 µg PNA mg?1DNPs. These systems are used for in vitro studies to evaluate the kinetic release, biocompatibility, cellular uptake, and activity on different cancer cells expressing high levels of PD-L1. The obtained results prove the safety of the NPs up to 200 µg mL?1 and their advantage for controlling and enhancing the PNA intracellular release as well as antitumor activity. Moreover, the downregulation of PD-L1 observed only with MDA-MB-231 cancer cells paves the way for targeted immunotherapy.",

keywords = "diatomite nanoparticles, gene therapy, peptide nucleic acids, redox-responsive, surface chemistry",

author = "Monica Terracciano and Flavia Fontana and Falanga, {Andrea Patrizia} and Stefano D'Errico and Giulia Torrieri and Francesca Greco and Chiara Tramontano and Ilaria Rea and Gennaro Piccialli and {De Stefano}, Luca and Giorgia Oliviero and Santos, {H{\'e}lder A.} and Nicola Borbone",

note = "https://doi.org/10.1002/smll.202204732",

year = "2022",

month = sep,

day = "11",

doi = "10.1002/smll.202204732",

language = "English",

volume = "18",

journal = "Small",

issn = "1613-6810",

publisher = "WILEY-V C H VERLAG GMBH",

number = "41",

}

Terracciano, M, Fontana, F, Falanga, AP, D'Errico, S, Torrieri, G, Greco, F, Tramontano, C, Rea, I, Piccialli, G, De Stefano, L, Oliviero, G, Santos, HA & Borbone, N 2022, 'Development of Surface Chemical Strategies for Synthesizing Redox-Responsive Diatomite Nanoparticles as a Green Platform for On-Demand Intracellular Release of an Antisense Peptide Nucleic Acid Anticancer Agent', Small, vol. 18, no. 41, 2204732. https://doi.org/10.1002/smll.202204732

Development of Surface Chemical Strategies for Synthesizing Redox-Responsive Diatomite Nanoparticles as a Green Platform for On-Demand Intracellular Release of an Antisense Peptide Nucleic Acid Anticancer Agent. / Terracciano, Monica; Fontana, Flavia; Falanga, Andrea Patrizia et al.
In: Small, Vol. 18, No. 41, 2204732, 11.09.2022.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Development of Surface Chemical Strategies for Synthesizing Redox-Responsive Diatomite Nanoparticles as a Green Platform for On-Demand Intracellular Release of an Antisense Peptide Nucleic Acid Anticancer Agent

AU - Terracciano, Monica

AU - Fontana, Flavia

AU - Falanga, Andrea Patrizia

AU - D'Errico, Stefano

AU - Torrieri, Giulia

AU - Greco, Francesca

AU - Tramontano, Chiara

AU - Rea, Ilaria

AU - Piccialli, Gennaro

AU - De Stefano, Luca

AU - Oliviero, Giorgia

AU - Santos, Hélder A.

AU - Borbone, Nicola

N1 - https://doi.org/10.1002/smll.202204732

PY - 2022/9/11

Y1 - 2022/9/11

N2 - Abstract Redox-responsive silica drug delivery systems are synthesized by aeco-friendly diatomite source to achieve on-demand release of peptide nucleic acid (PNA) in tumor reducing microenvironment, aiming to inhibit the immune checkpoint programmed cell death 1 receptor/programmed cell death receptor ligand 1 (PD-1/PD-L1) in cancer cells. The nanoparticles (NPs) are coated with polyethylene glycol chains as gatekeepers to improve their physicochemical properties and control drug release through the cleavable disulfide bonds (S?S) in a reductive environment. This study describes different chemical conditions to achieve the highest NPs? surface functionalization yield, exploring both multistep and one-pot chemical functionalization strategies. The best formulation is used for covalent PNA conjugation via the S?S bond reaching a loading degree of 306 ± 25 µg PNA mg?1DNPs. These systems are used for in vitro studies to evaluate the kinetic release, biocompatibility, cellular uptake, and activity on different cancer cells expressing high levels of PD-L1. The obtained results prove the safety of the NPs up to 200 µg mL?1 and their advantage for controlling and enhancing the PNA intracellular release as well as antitumor activity. Moreover, the downregulation of PD-L1 observed only with MDA-MB-231 cancer cells paves the way for targeted immunotherapy.

AB - Abstract Redox-responsive silica drug delivery systems are synthesized by aeco-friendly diatomite source to achieve on-demand release of peptide nucleic acid (PNA) in tumor reducing microenvironment, aiming to inhibit the immune checkpoint programmed cell death 1 receptor/programmed cell death receptor ligand 1 (PD-1/PD-L1) in cancer cells. The nanoparticles (NPs) are coated with polyethylene glycol chains as gatekeepers to improve their physicochemical properties and control drug release through the cleavable disulfide bonds (S?S) in a reductive environment. This study describes different chemical conditions to achieve the highest NPs? surface functionalization yield, exploring both multistep and one-pot chemical functionalization strategies. The best formulation is used for covalent PNA conjugation via the S?S bond reaching a loading degree of 306 ± 25 µg PNA mg?1DNPs. These systems are used for in vitro studies to evaluate the kinetic release, biocompatibility, cellular uptake, and activity on different cancer cells expressing high levels of PD-L1. The obtained results prove the safety of the NPs up to 200 µg mL?1 and their advantage for controlling and enhancing the PNA intracellular release as well as antitumor activity. Moreover, the downregulation of PD-L1 observed only with MDA-MB-231 cancer cells paves the way for targeted immunotherapy.

KW - diatomite nanoparticles

KW - gene therapy

KW - peptide nucleic acids

KW - redox-responsive

KW - surface chemistry

U2 - 10.1002/smll.202204732

DO - 10.1002/smll.202204732

M3 - Article

SN - 1613-6810

VL - 18

JO - Small

JF - Small

IS - 41

M1 - 2204732

ER -