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Dually responsive mesoporous silica nanoparticles regulated by upper critical solution temperature polymers for intracellular drug delivery.

ABSTRACT: We synthesized a new type of upper critical solution temperature (UCST) thermally responsive polymers (TRPs) with varying responsive temperatures (cloud points). We then grafted one of the TRPs with a cloud point of 42°C on the surface of mesoporous silica nanoparticles (MSN) using disulfide bonds to achieve a novel, dual responsive release system. With this system, the cargo release profiles are responsive to both temperature and reducing agents. When loaded with doxorubicin hydrochloride (DOX), the system could deliver DOX into breast cancer cells (SK-BR-3) in a controlled fashion and present high toxicity.

SUBMITTER: Hei M

PROVIDER: S-EPMC5730344 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Dually responsive mesoporous silica nanoparticles regulated by upper critical solution temperature polymers for intracellular drug delivery.

Hei Mingyang M Wang Jun J Wang Kelly K Zhu Weiping W Ma Peter X PX

Journal of materials chemistry. B 20171121 48

We synthesized a new type of upper critical solution temperature (UCST) thermally responsive polymers (TRPs) with varying responsive temperatures (cloud points). We then grafted one of the TRPs with a cloud point of 42°C on the surface of mesoporous silica nanoparticles (MSN) using disulfide bonds to achieve a novel, dual responsive release system. With this system, the cargo release profiles are responsive to both temperature and reducing agents. When loaded with doxorubicin hydrochloride (DOX) ...[more]

PMID: 29250331

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Project description:A redox-responsive nanocarrier is a promising strategy for the intracellular drug release because it protects the payload, prevents its undesirable leakage during extracellular transport, and favors site-specific drug delivery. In this study, we developed a novel redox responsive core-shell structure nanohydrogel prepared by a water in oil nanoemulsion method using two biocompatible synthetic polymers: vinyl sulfonated poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate)-polyethylene glycol-poly(N-(2-hydroxypropyl) methacrylamide mono/dilactate) triblock copolymer, and thiolated hyaluronic acid. The influence on the nanohydrogel particle size and distribution of formulation parameters was investigated by a three-level full factorial design to optimize the preparation conditions. The surface and core-shell morphology of the nanohydrogel were observed by scanning electron microscope, transmission electron microscopy, and further confirmed by Fourier transform infrared spectroscopy and Raman spectroscopy from the standpoint of chemical composition. The redox-responsive biodegradability of the nanohydrogel in reducing environments was determined using glutathione as reducing agent. A nanohydrogel with particle size around 250 nm and polydispersity index around 0.1 is characterized by a thermosensitive shell which jellifies at body temperature and crosslinks at the interface of a redox-responsive hyaluronic acid core via the Michael addition reaction. The nanohydrogel showed good encapsulation efficiency for model macromolecules of different molecular weight (93% for cytochrome C, 47% for horseradish peroxidase, and 90% for bovine serum albumin), capacity to retain the peroxidase-like enzymatic activity (around 90%) of cytochrome C and horseradish peroxidase, and specific redox-responsive release behavior. Additionally, the nanohydrogel exhibited excellent cytocompatibility and internalization efficiency into macrophages. Therefore, the developed core-shell structure nanohydrogel can be considered a promising tool for the potential intracellular delivery of different pharmaceutical applications, including for cancer therapy.

Project description:Nanoparticle-based drug delivery systems are among the most popular research topics in recent years. Compared with traditional drug carriers, mesoporous silica nanoparticles (MSN) offer modifiable surfaces, adjustable pore sizes and good biocompatibility. Nanoparticle-based drug delivery systems have become a research direction for many scientists. With the active target factionalized, scientists could deliver drug carriers into cancer cells successfully. However, drugs in cancer cells could elicit drug resistance and induce cell exocytosis. Thus, the drug cannot be delivered to its pharmacological location, such as the nucleus. Therefore, binding the cell membrane and the nuclear target on the nanomaterial so that the anticancer drug can be delivered to its pharmacological action site is our goal. In this study, MSN-EuGd was synthesized by doping Eu3+ and Gd3+ during the synthesis of MSN. The surface of the material was then connected to the TAT peptide as the nucleus target for targeting the cancer nucleus and then loaded with the anticancer drug camptothecin (CPT). Then, the surface of MSN-EuGd was bonded to the hyaluronic acid as an active target and gatekeeper. With this system, it is possible and desirable to achieve dual imaging and dual targeting, as well as to deliver drugs to the cell nucleus under a hyaluronidase-controlled release. The experimental approach is divided into three parts. First, we conferred the material with fluorescent and magnetic dual-imaging property by doping Eu3+ and Gd3+ into the MSN. Second, modification of the cell membrane target molecule and the nucleus target molecule occurred on the surface of the nanoparticle, making the nanoparticle a target drug carrier. Third, the loading of drug molecules into the carrier gave the entire carrier a specific target profile and enabled the ability to treat cancer. In this study, we investigated the basic properties of the drug carrier, including physical properties, chemical properties, and in vitro tests. The result showed that we have successfully designed a drug delivery system that recognizes normal cells and cancer cells and has good anticancer effects.

Dataset Information

Dually responsive mesoporous silica nanoparticles regulated by upper critical solution temperature polymers for intracellular drug delivery.

Publications

Dually responsive mesoporous silica nanoparticles regulated by upper critical solution temperature polymers for intracellular drug delivery.

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