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Folic Acid-Terminated Poly(2-Diethyl Amino Ethyl Methacrylate) Brush-Gated Magnetic Mesoporous Nanoparticles as a Smart Drug Delivery System.

ABSTRACT: Currently, chemotherapy is an important method for the treatment of various cancers. Nevertheless, it has many limitations, such as poor tumour selectivity and multi-drug resistance. It is necessary to improve this treatment method by incorporating a targeted drug delivery system aimed to reduce side effects and drug resistance. The present work aims to develop pH-sensitive nanocarriers containing magnetic mesoporous silica nanoparticles (MMSNs) coated with pH-responsive polymers for tumour-targeted drug delivery via the folate receptor. 2-Diethyl amino ethyl methacrylate (DEAEMA) was successfully grafted on MMSNs via surface initiated ARGET atom transfer radical polymerization (ATRP), with an average particle size of 180 nm. The end groups of poly (2-(diethylamino)ethyl methacrylate) (PDEAEMA) brushes were converted to amines, followed by a covalent bond with folic acid (FA) as a targeting agent. FA conjugated to the nanoparticle surface was confirmed by X-ray photoelectron spectroscopy (XPS). pH-Responsive behavior of PDEAEMA brushes was investigated by Dynamic Light Scattering (DLS). The nanoparticles average diameters ranged from ca. 350 nm in basic media to ca. 650 in acidic solution. Multifunctional pH-sensitive magnetic mesoporous nanoparticles were loaded with an anti-cancer drug (Doxorubicin) to investigate their capacity and long-circulation time. In a cumulative release pattern, doxorubicin (DOX) release from nano-systems was ca. 20% when the particle exposed to acidic media, compared to ca. 5% in basic media. The nano-systems have excellent biocompatibility and are minimally toxic when exposed to MCF-7, and -MCF-7 ADR cells.

SUBMITTER: Beagan AM

PROVIDER: S-EPMC7795197 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Folic Acid-Terminated Poly(2-Diethyl Amino Ethyl Methacrylate) Brush-Gated Magnetic Mesoporous Nanoparticles as a Smart Drug Delivery System.

Beagan Abeer M AM Alghamdi Ahlam A AA Lahmadi Shatha S SS Halwani Majed A MA Almeataq Mohammed S MS Alhazaa Abdulaziz N AN Alotaibi Khalid M KM Alswieleh Abdullah M AM

Polymers 20201225 1

Currently, chemotherapy is an important method for the treatment of various cancers. Nevertheless, it has many limitations, such as poor tumour selectivity and multi-drug resistance. It is necessary to improve this treatment method by incorporating a targeted drug delivery system aimed to reduce side effects and drug resistance. The present work aims to develop pH-sensitive nanocarriers containing magnetic mesoporous silica nanoparticles (MMSNs) coated with pH-responsive polymers for tumour-targ ...[more]

PMID: 33375759

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Project description:Conventional cryopreservation solutions rely on the addition of organic solvents such as DMSO or glycerol, but these do not give full recovery for all cell types, and innovative cryoprotectants may address damage pathways which these solvents do not protect against. Macromolecular cryoprotectants are emerging, but there is a need to understand their structure-property relationships and mechanisms of action. Here we synthesized and investigated the cryoprotective behavior of sulfoxide (i.e., "DMSO-like") side-chain polymers, which have been reported to be cryoprotective using poly(ethylene glycol)-based polymers. We also wanted to determine if the polarized sulfoxide bond (S+O- character) introduces cryoprotective effects, as this has been seen for mixed-charge cryoprotective polyampholytes, whose mechanism of action is not yet understood. Poly(2-(methylsulfinyl)ethyl methacrylate) was synthesized by RAFT polymerization of 2-(methylthio)ethyl methacrylate and subsequent oxidation to sulfoxide. A corresponding N-oxide polymer was also prepared and characterized: (poly(2-(dimethylamineoxide)ethyl methacrylate). Ice recrystallization inhibition assays and differential scanning calorimetry analysis show that the sulfoxide side chains do not modulate the frozen components during cryopreservation. In cytotoxicity assays, it was found that long-term (24 h) exposure of the polymers was not tolerated by cells, but shorter (30 min) incubation times, which are relevant for cryopreservation, were tolerated. It was also observed that overoxidation to the sulfone significantly increased the cytotoxicity, and hence, these materials require a precision oxidation step to be deployed. In suspension cell cryopreservation investigations, the polysulfoxides did not increase cell recovery 24 h post-thaw. These results show that unlike hydrophilic backboned polysulfides, which can aid cryopreservation, the installation of the sulfoxide group onto a polymer does not necessarily bring cryoprotective properties, highlighting the challenges of developing and discovering macromolecular cryoprotectants.

Dataset Information

Folic Acid-Terminated Poly(2-Diethyl Amino Ethyl Methacrylate) Brush-Gated Magnetic Mesoporous Nanoparticles as a Smart Drug Delivery System.

Publications

Folic Acid-Terminated Poly(2-Diethyl Amino Ethyl Methacrylate) Brush-Gated Magnetic Mesoporous Nanoparticles as a Smart Drug Delivery System.

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