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. 2022 Sep 14;21(1):e130474.
doi: 10.5812/ijpr-130474. eCollection 2022 Dec.

Enzyme and Thermo Dual-stimuli Responsive DOX Carrier Based on PNIPAM Conjugated Mesoporous Silica

Seyyed Mostafa Ebrahimi  1 , Mahdieh Karamat Iradmousa  1 , Mahtab Rashed  1 , Yousef Fattahi  2   3 , Yalda Hosseinzadeh Ardakani  3 , Saeed Bahadorikhalili  4 , Reza Bafkary  2 , Mohammad Erfan  1 , Rassoul Dinarvand  2   3 , Arash Mahboubi  1
Affiliations

Enzyme and Thermo Dual-stimuli Responsive DOX Carrier Based on PNIPAM Conjugated Mesoporous Silica

Seyyed Mostafa Ebrahimi et al. Iran J Pharm Res. .

Abstract

Background: Stimuli-responsive drug delivery systems have been proven to be a promising strategy to enhance tumor localization, overcome multidrug resistance (MDR), and reduce the side effects of chemotherapy agents.

Objectives: In this study, a temperature and redox dual stimuli-responsive system using mesoporous silica nanoparticles (MSNs) for targeted delivery of doxorubicin (DOX) was developed.

Methods: Mesoporous silica nanoparticles were capped with poly(N-isopropylacrylamide) (PNIPAM), a thermo-sensitive polymer, with atom transfer radical polymerization (ATRP) method, via disulfide bonds (DOX-MSN-S-S-PNIPAM) to attain a controlled system that releases DOX under glutathione-rich (GSH-rich) environments and temperatures above PNIPAM's lower critical solution temperature (LCST). Morphological and physicochemical properties of the nanoparticles were indicated using transmission electron microscopy (TEM), dynamic light scattering (DLS), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and Brunauer-Emmett-Teller (BET). The drug release tests were performed at 25°C and 41°C in the absence and presence of the DTT, and the obtained results confirmed the synergic effect of temperature and reductive agent on a dual responsive release profile with a 73% cumulative release at 41°C and reductive environment during 240 min.

Results: The average loaded drug content and encapsulation efficacy were reported as 42% and 29.5% at the drug: nanoparticle ratio of 1.5: 1. In vitro cytotoxicity assays on MCF-7 cell lines indicated significant viability decreased in cells exposed to DOX-MSN-S-S-PNIPAM compared to the free drug (DOX).

Conclusions: Based on the results, DOX-MSN-S-S-PNIPAM has shown much more efficiency with stimuli-responsive properties in comparison to DOX on MCF-7 cancer cell lines.

Keywords: ATRP Polymerization; Cancer; Drug Delivery; Nanoparticles; Stimuli-Responsive.

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Conflict of interest statement

Conflict of Interests: The authors declare that they have no conflict of interests.

Figures

Figure 1.
Figure 1.. Synthesis steps of mesoporous silica nanoparticle (MSN)-S-S-Poly(N-isopropylacrylamide) (PNIPAM)
Figure 2.
Figure 2.. A schematic pattern of synthesizing stimuli-responsive mesoporous silica and cellular uptake and doxorubicin (DOX) release of mesoporous silica nanoparticle (MSN)-S-S-poly(N-isopropylacrylamide) (PNIPAM). (1) (3-glycidyloxypropyl)trimethoxysilane (GPTMS); (2) cystamine; (3) 2-bromoisobutyryl bromide (BIBB); (4) (N-isopropylacrylamide)-co-methacrylic acid (NIPAM)/hydroxy ethyl methacrylate (HEMA); (5) DOX-loading at low temperature; (6) cytotoxicity assays
Figure 3.
Figure 3.. Fourier transform infrared spectra (FTIR) spectra of different steps of synthesizing mesoporous silica nanoparticle (MSN)-S-S-poly(N-isopropylacrylamide) (PNIPAM)
Figure 4.
Figure 4.. X-ray diffraction (XRD) pattern of mesoporous silica nanoparticle (MSN) (Mobil Composition of Matter No. 41 (MCM-41))
Figure 5.
Figure 5.. Nitrogen adsorption/desorption of the mesoporous silica nanoparticle (MSN) and MSN-S-S-poly(N-isopropylacrylamide) (PNIPAM) components
Figure 6.
Figure 6.. Thermogravimetric analysis (TGA) curves of mesoporous silica nanoparticle (MSN), MSN-2-bromoisobutyryl bromide (BIBB), and MSN-S-S-poly(N-isopropylacrylamide) (PNIPAM)
Figure 7.
Figure 7.. Differential scanning calorimetry measurement of the mesoporous silica nanoparticle (MSN)-S-S-poly(N-isopropylacrylamide) (PNIPAM)
Figure 8.
Figure 8.. Transmission electron microscopy images of A, mesoporous silica nanoparticle (MSN) and; B, MSN-S-S-poly(N-isopropylacrylamide) (PNIPAM)
Figure 9.
Figure 9.. In vitro release profile of doxorubicin (DOX) from DOX-mesoporous silica nanoparticle (MSN)-S-S-poly(N-isopropylacrylamide) (PNIPAM) in two temperatures of 25°C and 41°C with and without reducing agent of dithiothreitol (DTT)
Figure 10.
Figure 10.. The cytotoxicity of doxorubicin (DOX) and DOX-mesoporous silica nanoparticle (MSN)-S-S-poly(N-isopropylacrylamide) (PNIPAM) in different concentrations against Michigan Cancer Foundation-7 (MCF-7) cell line. Results were expressed as mean ± SD (n = 5); significance was calculated by ANOVA (* P ≤ 0.05).
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References

    1. Tacar O, Sriamornsak P, Dass CR. Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. J Pharm Pharmacol. 2013;65(2):157–70. doi: 10.1111/j.2042-7158.2012.01567.x. - DOI - PubMed
    1. Di Martino A, Kucharczyk P, Capakova Z, Humpolicek P, Sedlarik V. Chitosan-based nanocomplexes for simultaneous loading, burst reduction and controlled release of doxorubicin and 5-fluorouracil. Int J Biol Macromol. 2017;102:613–24. doi: 10.1016/j.ijbiomac.2017.04.004. - DOI - PubMed
    1. Christowitz C, Davis T, Isaacs A, van Niekerk G, Hattingh S, Engelbrecht AM. Mechanisms of doxorubicin-induced drug resistance and drug resistant tumour growth in a murine breast tumour model. BMC Cancer. 2019;19(1):757. doi: 10.1186/s12885-019-5939-z. - DOI - PMC - PubMed
    1. Ye Q, Liu K, Shen Q, Li Q, Hao J, Han F, et al. Reversal of Multidrug Resistance in Cancer by Multi-Functional Flavonoids. Front Oncol. 2019;9:487. doi: 10.3389/fonc.2019.00487. - DOI - PMC - PubMed
    1. Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B. The Different Mechanisms of Cancer Drug Resistance: A Brief Review. Adv Pharm Bull. 2017;7(3):339–48. doi: 10.15171/apb.2017.041. - DOI - PMC - PubMed

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