Glutathione Mediated Size‐Tunable UCNPs‐Pt(IV)‐ZnFe₂O₄ Nanocomposite for Multiple Bioimaging Guided Synergetic Therapy

Abstract

Here a multifunctional nanoplatform (upconversion nanoparticles (UCNPs)-platinum(IV) (Pt(IV))-ZnFe O , denoted as UCPZ) is designed for collaborative cancer treatment, including photodynamic therapy (PDT), chemotherapy, and Fenton reaction. In the system, the UCNPs triggered by near-infrared light can convert low energy photons to high energy ones, which act as the UV-vis source to simultaneously mediate the PDT effect and Fenton's reaction of ZnFe O nanoparticles. Meanwhile, the Pt(IV) prodrugs can be reduced to high virulent Pt(II) by glutathione in the cancer cells, which can bond to DNA and inhibit the copy of DNA. The synergistic therapeutic effect is verified in vitro and in vivo results. The cleavage of Pt(IV) from UCNPs during the reduction process can shift the larger UCPZ nanoparticles (NPs) to the smaller ones, which promotes the enhanced permeability and retention (EPR) and deep tumor penetration. In addition, due to the inherent upconversion luminescence (UCL) and the doped Yb and Fe in UCPZ, this system can serve as a multimodality bioimaging contrast agent, covering UCL, X-ray computed tomography, magnetic resonance imaging, and photoacoustic. A smart all-in-one imaging-guided diagnosis and treatment system is realized, which should have a potential value in the treatment of tumor.

Designing Stimuli‐Responsive Upconversion Nanoparticles that Exploit the Tumor Microenvironment

“…This conversion initiated PDT and the Fenton reaction, along with a simultaneous conversion of Pt(IV) to the DNA binding Pt(II) as a result of the elevated amounts of glutathione (GSH) present in cancer cells. [ 51 ] Importantly, again in 2018, Xu et al developed a Mn‐containing UCNP encapsulating doxorubicin which concomitantly responded to the lower reductive potential and low pH of the tumor microenvironment for theranostic use. Therein, Mn‐O was disrupted by GSH at in the acidic environment, enabling rupture of the nanocarriers to ensure enhanced tumor penetration and effective release of the drug.…”

Chemodynamic Therapy: Tumour Microenvironment‐Mediated Fenton and Fenton‐like Reactions

“…These results confirmed the capacity of AFeNPs for selective ferrous ion release, thus ensuring the efficiency of CDT. In addition, many other iron‐based nanomaterials, including Fe oxides, [FeO(OH) n ], and M(Sn,Mn)Fe 2 O 4 have also been introduced as CDT agents, but none have focused on increasing the release of the catalytic Fe 2+ ions.…”

Chemodynamic Therapy: Tumour Microenvironment‐Mediated Fenton and Fenton‐like Reactions

“…[29] Fori nstance,o ur group synthesized amorphous Fe 0 nanoparticles (AFeNPs) (Figure 1a), [25] which were rapidly ionized in an acidic TME to release more Fe 2+ ions than Fe 0 nanocrystals (FeNCs) for CDT because it had the reactive nature of metallic glasses.A sp resented in Figure 1b,c, the release rate of ferrous ions from the AFeNPs reached 57 %at ap Ho f6 .5 and 100 %a tapH of 5.4 within 6h,w hich were much higher than those observed for the FeNCs.M oreover, both AFeNPs and FeNCs tended to slowly release ferrous ions at aneutral pH. These results confirmed the capacity of AFeNPs for selective ferrous ion release,t hus ensuring the efficiency of CDT.I na ddition, many other iron-based nanomaterials,i ncluding Fe oxides, [30][31][32] [FeO(OH) n ], [33] and M(Sn,Mn)Fe 2 O 4 [34,35] have also been introduced as CDT agents,b ut none have focused on increasing the release of the catalytic Fe 2+ ions.…”