Mesoporous Silica Nanoparticles-Based Stimuli-Responsive Drug Delivery Systems Gated by Polymers †

doi:10.7503/cjcu20190572

Abstract

Abstract:

With the rapid development ofmaterials science and nanotechnology, stimuli-responsive drug delivery systems(DDS) for cancer therapy have drawn more and more attention. Mesoporous silica nanoparticles(MSNs) possess numerous advantages, such as large loading capacity, desirable biocompatibility, and various types of stimuli-responsiveness, which endowed them with significant roles in biomedical and related applications. Hybrid materials, particularly with MSNs as drug carriers and polymers as gatekeepers have emerged as promising DDS in recent years. In this review, we make an overview of such organic-inorganic hybrid materials for controlled drug release, with themain focus on the use of three types of polymer gating systems on the surfaces of MSNs, which include polymer brushes, polymers networks, and polymer coatings. On the basis of the types of connections, covalent or non-covalent, between these gatekeepers and drug carriers, we showcase the controlled drug release properties of these hybrid materials in response to a variety of external stimuli. The challenges and chances of hybrid nanocarriers constructed from MSNs and polymers are also discussed.

Key words: Stimuli-responsive drug delivery system, Macromolecule, Polymer brushe, Polymer crosslinked network, Polymer coating, Nanovalve, Supramolecular chemistry, Targeted drug delivery, Mesoporous silica nanoparticles

CLC Number:

O631

TrendMD:

WANG Xinghuo,TANG Jun,YANG Yingwei. Mesoporous Silica Nanoparticles-Based Stimuli-Responsive Drug Delivery Systems Gated by Polymers ^†[J]. Chem. J. Chinese Universities, 2020, 41(1): 28.

Figures/Tables 12

Fig.1 Functional polymers served as gatekeepers including polymer brushes(A), polymernetworks(B) and polymer coatings(C)

Fig.2 Schematic illustration of preparation of polymer brushes by “grafting to” method(A) and “grafting from” method(B)

Fig.3 Schematic representation of the preparation process of Rh6G-loaded PDMAEMA-grafted MSN(Rh6G@MSN-PDMAEMA) via SI-ATRP and its pH-responsive behavior[60](A) and illustration of the pH-responsive drug delivery system of MSNs-PLH-PEG[64](B) (A) Copyright 2016, MDPI; (B) copyright 2017, Elsevier Ltd.

Fig.4 Redox-responsive cargo release systems based onmPEG brushes decorated MSNs[69](A), PEG-PCL brushes-functionalized MSNs(MSN-SS-PCL-PEG)[71](B) and therapeutic peptides-gated MSNs(DOX@TTSTMSN)[72](C) (A) Copyright 2015, Elsevier Ltd. (B) copyright 2013, Royal Society of Chemistry; (C) copyright 2016, Royal Society of Chemistry.

Fig.5 Drug loading and release triggered by temperature (A) Schematic illustration of PNIPAAm grafting onto the surface of MSNs for drug delivery[73]; (B) schematic illustration of dual-responsive MSNs gated byPNIPAAm-PBAPAR [77]; (C) UCST TRP-modified MSN system: (i) schematic illustration of the preparation and intracellular uptake; (ii) turbidity curve of TRP1, TRP2, and TRP3(1%) in PBS; (iii) characterization of TRP1, TRP2 and TRP3 of different UCSTs[79]. (A) Copyright 2008, American Chemical Society; (B) copyright 2018, Elsevier Ltd.; (C) copyright 2017, Royal Society of Chemistry.

Fig.6 Drug loading and release triggered by light[84] (A) Schematic representation for the structure of HMSNs-PDEAEMA and the different mechanisms of triggered release; (B) synthetic route of tripleresponsive HMSNs-PDEAEMA via SI-ATRP. in vitro DOX release profiles of HMSNs@DOX; (C) triggered by UV light at pH=7.4; (D) at 37 ℃ under different pH values without and with DTT. Copyright 2015, American Chemical Society.

Fig.7 Drug loading and release triggered by ultrasound[88] (A) Schematic illustration of the temperature/ultrasound dual-responsiveness; (B) synthetic route to PMEO2MA-PTHPMA-MSN; (C) ultrasound-triggered bond cleavage of PMEO2MA-PTHPMA into PMEO2MA-PMAA and tetrahydropyranol(THP-ol); (D) release profile of fluorescein from hybrid-MSNs in PBS uponultrasound treatment(10 min and 1.3 MHz, 100 W)(a) and without ultrasound(b). Copyright 2015, American Chemical Society.

Fig.8 Covalent bond cross-linked polymer networks served as gatekeepers (A) Schematic illustration ofthe synthetic route of MSN-PGMA and cystamine cross-linked PGMA networks on MSNs and Rh6G release in response to pH and GSH; (B) release profiles of cross-linked PSSGMA in PBS buffers of different pH values; (C) release profiles of polymer brushes PSGMA in PBS buffers of different pH values[91]. Copyright 2016, Royal Society of Chemistry.

Fig.9 Non-covalent bond cross-linked polymer networks served as gatekeepers (A) Schematic diagram of (i) pH and GSH dual-responsive dynamic cross-linked supramolecular networks on MSNs; (ii) synthetic route of MSN-SS-(EDA-PGOHMA) and its assembly with CB[7][100]. (B) Schematic illustration of (i) the preparation of polymer brush decorated MOFs; (ii) drug release behavior of the MOF-based nanoparticles[101]. (A) Copyright 2015, American Chemical Society; (B) Copyright 2018, Wiley-VCH.

Fig.10 Schematic illustration of the preparation of MSN-SS-HA and its dual-stimuli responsive drug delivery[102] (A) Synthesis of drug-loaded MSN-SS-HA; (B) magnified image of pore structure upon grafting of HA; (C) cell uptake through CD44 receptor-mediated interaction. Copyright 2015, Elsevier Ltd.

Fig.11 Schematic representation of the preparation process of RhB-loaded MSN@PGMA-CD and its cargo release in response to UV light or competitive binding[104] Copyright 2014, Royal Society of Chemistry.

Fig.12 Schematic representation of nanoassembly constructed via LBL assembly(A), colony forming units(CFU) for S. aureus and E. coli treated with nanoassembly before and after addition of adamantaneamine(AD) on LB agar plate(B) and illustration of drug release triggered by addition of AD(C)[106] Copyright 2017, American Chemical Society.

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