Controllably Switched Drug Release from Successively Dual‐Targeted Nanoreservoirs

Abstract

The development of a nanocarrier with a capacity of releasing therapeutic agent "on demand" is of great importance for enhancing drug efficacy and reducing its side effect. Here, a multifunctional mesoporous silica nanoparticle is presented for cancer therapy. This nanoparticle can not only successively target tumor tissue and tumor cells but also has a function of controllably switching the drug release. Low molecular weight poly(ethyleneimine) segments, which are decorated on the surface of magnetic mesoporous silica nanoparticle with disulfide bonds, are chemically cross-linked, leading to the mesopores being "closed" in blood circulation but being "open" via taking off the coating in cytoplasm. As a result, the encapsulated drug can be kept in nanoparticles in the normal conditions, while be rapidly released in a reduction condition. In vivo antitumor activity demonstrates that this nanoparticle has the highest safety to body and the best therapeutic efficacy against tumors. Therefore, this work presents a good example of rational design of nanocarriers for highly effective cancer therapy.

Advances in Magnetic Nanoparticles for Biomedical Applications

“…A multifunctional magnetic mesoporous Fe 3 O 4 /silica nanoparticle with both a successive dual‐targeting (both active and magnetic, Figure ) ability and a controllably switched drug release options was presented in ref. .…”

“…Schematic representation of doxorubicin (DOX)‐loaded cross‐linked magnetic mesoporous silica NPs MMSN‐S2‐ poly(ethyleneimine) (PEI)‐PEG‐ phenylboronic acid (PBA) reservoirs being consecutively targeted to the tumor site through the magnetic targeting enhanced permeability and retention effect and NanoEL, and the SA‐positive HepG2 cells by the active‐targeting, succeeding a fast drug release by GSH stimulus in the cytoplasm. Reproduced with permission …”

Emerging and Innovative Theranostic Approaches for Mesoporous Silica Nanoparticles in Hepatocellular Carcinoma: Current Status and Advances

“…In another way, magnetic mesoporous silica nanoparticles (M-MSNs) with superior magnetic properties maintaining the excellent advantages of MSNs could achieve magnetic-mediated targeting functions under external magnetic fields (EMFs) (Shao D. et al, 2016;Wang Y. et al, 2016;Tang et al, 2017). The targeting capacity guided by EMFs including two aspects: on the one hand, M-MSNs would mainly accumulation around the tumor site under the EMFs, which could apply a magnetic force on nanoparticles to enhance the EPR effect and overcome the drag experienced in the blood flow (Thorat et al, 2019a); on another hand, EMFs effect could enhance endocytosis of the tumor cells.…”

“…SMMC-7721 mice model, H22 mice model Chen et al, 2012;Liao et al, 2014;Yu et al, 2015;Zeng et al, 2016;Fei et al, 2017;Li et al, 2018b Transferrin cells . The disulfide bond which could be cleaved by GSH is widely used to connect the gatekeepers and MSNs Tang et al, 2017;Wang J.K. et al, 2017). In one study, the surfaces of MSNs were functionalized by cytochrome c (CytC) via disulfide bonds, which would be rapidly cleaved in HCC cells to release the loaded drug.…”

Polymer-Based Nanocarriers for Co-Delivery and Combination of Diverse Therapies against Cancers

“…Due to the hydrophilic moiety such as polyethylene glycol (PEG) or chitosan (CTS), nanocarriers with several hundred nanometers diameter may increase the bioavailability and extend blood circulation time of insoluble drugs [ 39 , 40 , 41 ]. According to the enhanced permeability and retention (EPR) effect, nanocarriers have passive targeting property (tend to enter tumors from irregular microvasculature and stay there for a longer period than small molecule drugs) [ 42 , 43 ]. Equipped with targeting ligands, nanocarriers are imparted with active targeting property (tend to actively accumulate in specific tumor tissues), reducing systematic toxicity and enhancing therapeutic effects [ 44 , 45 ].…”