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  • d Department of Stomatology The First A liated Hospital of

    2019-09-23

    d Department of Stomatology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, PR China
    e Hefei Cancer Hospital, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, PR China
    f School of Life Sciences, Anhui Agricultural University, Hefei 230036, PR China
    Keywords:
    Microenvironment-responsive
    Degradable
    Combinatorial therapy
    Magnetic resonance imaging
    Nanotheranostics 
    In this work, a tumor microenvironment (TME)-responsive biodegradable [email protected] nanoplatform for dual-mode magnetic resonance imaging (MRI)-guided combinatorial cancer therapy was constructed. Fe3O4 nanoparticles decorated on the surface of MnSiO3 could effectively obstruct the pores of MnSiO3 and reduce the leakage of anticancer drugs under physiological conditions. The structure of the nanoplatform was broken under the weakly acidic and high-concentration glutathione conditions in the TME, resulting in the separation of the Fe3O4 nanoparticles from the nanoplatform and rapid drug release. In addition, the exfoliated Fe3O4 and re-leased Mn2+ can help reduce the interference between their T1 and T2 contrast abilities, resulting in dual-mode MRI contrast enhancement. Furthermore, during the exfoliation process of the Fe3O4 nanocrystals, the catalytic activity of the Fe3O4 nanocrystals toward a Fenton-like reaction within cancer Prostaglandin J2 could be improved because of the increase in specific surface area, which led to the generation of highly toxic hydroxyl radicals and induced HeLa cell apoptosis. The nanoplatform also displayed excellent T1-T2 dual-mode MRI contrast enhancement and anticancer activity in vivo with reduced systemic toxicity. Thus, this multifunctional nanoplatform could be a potential nanotheranostic for dual-mode MRI-guided combinatorial cancer therapy.
    1. Introduction
    Nanoparticle ensembles with the collective properties of individual nanoparticles hold great potential as multifunctional drug delivery systems (DDS) and bioimaging contrast agents [1–4]. However, the clinical translation of these nanoplatforms is greatly limited by their long-term safety issues, including toxicity, degradation, and metabo-lism of the nanomaterial in the body [5–8]. The biocompatibility and biodistribution of nanoparticles in vivo could be partly optimized by tailoring their surface chemistry properties (e.g., PEGylation) [9–11]. Nevertheless, this approach does not have a decisive effect on im-proving nanomaterial metabolism. Fundamentally, the particle size
    plays a vital role in nanoparticle biodistribution [12,13]. Generally, nanoparticles that are less than 10 nm in size can be quickly excreted from the body via renal filtration [14,15], but these particles hardly accumulate in tumor tissue by passive targeting [16,17]. In addition, a large size (100–200 nm) can improve the retention time and the accu-mulation of particles at the tumor site via the enhanced permeability and retention (EPR) effect [18,19], but it limits the penetration depth of particles into the tumor parenchyma [20,21] and is detrimental to the degradation and excretion of nanoparticles in vivo [22,23]. Therefore, development of nanomaterials with suitable size and degradability is necessary to enhance the accumulation and penetration depth of par-ticles at the tumor site and thus achieve good therapeutic effects and
    ∗ Corresponding author. ∗∗ Corresponding author. Department of Dental Implant Center, Stomatologic Hospital & College, Anhui Medical University, Key Laboratory of Oral Diseases Research of Anhui Province, Hefei 230032, PR China.
    E-mail addresses: [email protected] (D. Zou), [email protected] (Z. Wu).