A Drug‐Self‐Gated Mesoporous Antitumor Nanoplatform Based on pH‐Sensitive Dynamic Covalent Bond

Zeng, Xiaowei; Liu, Gan; Tao, Wei; Ma, Yue; Zhang, Xudong; He, Fan; Pan, Jianming; Mei, Lin; Pan, Guoqing

doi:10.1002/adfm.201605985

Cited by 277 publications

(150 citation statements)

References 78 publications

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“…While at pH 6.5 (simulating tumor extracellular microenvironment), the DOX‐released percentage of the two PDA‐coated NPs reached about 37.4% and 38.9%, respectively. When the pH values decreased from 6.5 to 5.0 for simulating the environment of late endosomes/lysosomes, both of MSNs‐DOX@PDA and MSNs‐DOX@PDA‐TPGS exhibited a remarkably higher DOX release concentrations (51.6% and 47.7%, respectively). The conspicuous increase of DOX release of PDA‐modified NPs under acidic conditions suggested that upon decreasing the pH, PDA coating on the surfaces was partially removed, which unlocked the gate.…”

Section: Resultsmentioning

confidence: 99%

TPGS‐Functionalized Polydopamine‐Modified Mesoporous Silica as Drug Nanocarriers for Enhanced Lung Cancer Chemotherapy against Multidrug Resistance

Cheng

Liang

et al. 2017

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A nanocarrier system of d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)-functionalized polydopamine-coated mesoporous silica nanoparticles (NPs) is developed for sustainable and pH-responsive delivery of doxorubicin (DOX) as a model drug for the treatment of drug-resistant nonsmall cell lung cancer. Such nanoparticles are of desired particle size, drug loading, and drug release profile. The surface morphology, surface charge, and surface chemical properties are also successfully characterized by a series of techniques such as transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET) method, thermal gravimetric analysis (TGA), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FTIR). The normal A549 cells and drug-resistant A549 cells are employed to access the cytotoxicity and cellular uptake of the NPs. The therapeutic effects of TPGS-conjugated nanoparticles are evaluated in vitro and in vivo. Compared with free DOX and DOX-loaded NPs without TPGS ligand modification, MSNs-DOX@PDA-TPGS exhibits outstanding capacity to overcome multidrug resistance and shows better in vivo therapeutic efficacy. This splendid drug delivery platform can also be sued to deliver other hydrophilic and hydrophobic drugs.

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Section: Resultsmentioning

confidence: 99%

TPGS‐Functionalized Polydopamine‐Modified Mesoporous Silica as Drug Nanocarriers for Enhanced Lung Cancer Chemotherapy against Multidrug Resistance

Cheng

Liang

et al. 2017

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“…Outlets Capping with DOX : The outlets of mesoporous silica nanoparticles were capped with DOX using our previously published method with some modifications . 1 mg of DOX was predispersed in 1 mL of ethanol with the aid of sonication and then 2 mg of M‐R was added, followed by addition of sodium hydroxide aqueous solution (4.5 µL, 0.5 m ).…”

Section: Methodsmentioning

confidence: 99%

“…To prevent the leakage of siRNA, the pores of mesoporous silica should be blocked by a molecule gatekeeper. Our previous study reported a doxorubicin (DOX) molecularly gated strategy to control drug release by the formation of pH‐responsive benzoic–imine bonds on a benzaldehyde‐functionalized MSNs (M‐CHO) . This inspired us to load siRNA into a benzaldehyde‐functionalized mesoporous silica and then blocked it by DOX, finally achieving the codelivery of P‐gp siRNA and DOX.…”

Section: Introductionmentioning

confidence: 99%

A Multifunctional Nanoplatform against Multidrug Resistant Cancer: Merging the Best of Targeted Chemo/Gene/Photothermal Therapy

Cheng

Nie

Gao

et al. 2017

Adv Funct Materials

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Synergistic therapy that combines chemo-, gene-, or photothermal means shows great potential for enhancing the therapeutic effects on cancers. Tumor-targeted nanoparticles based on a doxorubicin (DOX)-gated mesoporous silica nanocore (MSN) encapsulated with permeability glycoprotein (P-gp) small interfering RNA (siRNA) and a polydopamine (PDA) outer layer for DOX loading and folic acid decoration are designed. The multifunctional nanoplatform tactfully integrates chemo-(DOX), gene-(P-gp siRNA), and photothermal (PDA layer) substances in one system. In vitro results reveal that DOX release behaviors are both pH-and thermal-responsive and the release of co-delivered P-gp siRNA is also pH-dependent due to the pH-cleavable DOX gatekeeper on MSN. In addition, due to the near-infrared light-responsive PDA outer layer and folic acid conjugation, the nanoparticles exhibit outstanding photothermal activity and selective cell targeting ability. Subsequently, in vitro and in vivo antitumor experiments both demonstrate the enhanced antitumor efficacy of the multifunctional nanoparticles, indicating the significance of synergistic therapy combining chemo-, gene-, and photothermal treatments in one system. Cancer Therapy

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“…[19,39] Here, we used a PTX prodrug as a GSHsensitive gatekeeper. [19,39] Here, we used a PTX prodrug as a GSHsensitive gatekeeper.…”

Section: Glutathione (Gsh)-dependent Drug Release and Nir-triggered Pmentioning

confidence: 99%

A Multifunctional Biodegradable Nanocomposite for Cancer Theranostics

Williams

Niu

et al. 2019

Advanced Science

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Theranostic formulations, integrating both diagnostic and therapeutic functions into a single platform, hold great potential for precision medicines. In this work, a biodegradable theranostic based on hollow mesoporous organosilica nanoparticles (HMONs) is reported and explored for ultrasound/photoacoustic dual‐modality imaging guided chemo‐photothermal therapy of cancer. The HMONs prepared are endowed with glutathione‐responsive biodegradation behavior by incorporating disulfide bonds into their framework. The nanoparticles are loaded with indocyanine green (ICG) and perfluoropentane (PFP). The former acts as a photothermal agent and the latter can generate bubbles for ultrasound imaging. A paclitaxel prodrug is developed to both serve as a redox‐sensitive gatekeeper controlling ICG release from the HMON pores and a chemotherapeutic. ICG generates mild hyperthermia upon exposure to an 808 nm laser, and this in turn leads to a liquid–gas phase transition of PFP, resulting in the generation of bubbles which can be used for ultrasound imaging. The platform is found to have excellent properties for both ultrasound and photoacoustic imaging. In addition, both in vitro and in vivo results show that the nanoparticles provide potent synergistic chemo‐photothermal therapy. The material developed in this work thus has great potential for exploitation in advanced cancer therapies.

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A Drug‐Self‐Gated Mesoporous Antitumor Nanoplatform Based on pH‐Sensitive Dynamic Covalent Bond

Cited by 277 publications

References 78 publications

TPGS‐Functionalized Polydopamine‐Modified Mesoporous Silica as Drug Nanocarriers for Enhanced Lung Cancer Chemotherapy against Multidrug Resistance

TPGS‐Functionalized Polydopamine‐Modified Mesoporous Silica as Drug Nanocarriers for Enhanced Lung Cancer Chemotherapy against Multidrug Resistance

A Multifunctional Nanoplatform against Multidrug Resistant Cancer: Merging the Best of Targeted Chemo/Gene/Photothermal Therapy

A Multifunctional Biodegradable Nanocomposite for Cancer Theranostics

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