Rational Modulation of BODIPY Photosensitizers to Design Metal–Organic Framework-Based NIR Nanocomposites for High-Efficiency Photodynamic Therapy in a Hypoxic Environment

Abstract

Photodynamic therapy (PDT) is a promising noninvasive treatment that has drawn great attention. However, the hypoxic environment in tumors seriously limits the therapeutic effect of oxygen-dependent chemicals and PDT. Herein, a versatile nanocomposite DF-BODIPY@ZIF-8 with oxygengenerating ability was developed based on zeolitic imidazolate framework-8 (ZIF-8) by loading the near-infrared photosensitizer DF-BODIPY to overcome hypoxia-induced drug resistance in cancer therapy. ZIF-8 can catalyze the decomposition of hydrogen peroxide in tumors and increase the dissolved oxygen concentration, resulting in a significant improvement in PDT efficacy. Additionally, we found that enhancing the electronegativity of substituents can effectively reduce the energy level difference (ΔE st ) between the minimum singlet state (S 1 ) and the lowest triplet state (T 1 ), leading to the enhancement of the singlet oxygen quantum yield. In vitro experiments suggested that DF-BODIPY@ZIF-8 indeed had a higher singlet oxygen quantum yield and better tumor cell phototoxicity than free DF-BODIPY. In vivo experiments also demonstrated that DF-BODIPY@ZIF-8 could effectively eliminate 4T1 tumors under light irradiation. Thus, we conclude that increasing the electronegativity of substituents and introducing a ZIF-8 material can effectively improve the singlet oxygen quantum yield and overcome the hypoxia limitations for high-efficiency PDT.

Understanding the role of metal–organic frameworks in cancer treatment

“…Shen et al developed a PDT system, namely DF-BODIPY@ZIF-8, with a NIR sensitizer (DF-BODIPY) and ZIF-8 MOF. 38 The DF-BODIPY moiety serves as the photosensitizer, in which the electron withdrawing group ( i.e. , trifluoromethyl group) can reduce the energy level difference (Δ E st in Fig.…”

Calcium-peroxide-mediated cascades of oxygen production and glutathione consumption induced efficient photodynamic and photothermal synergistic therapy

“…43 Zeolitic imidazolate framework-8 (ZIF-8), known as the most versatile subclass of metal–organic frameworks (MOFs) consisting of zinc and imidazole, possesses excellent properties such as non-toxicity, good dispersity and ultrahigh loading capacity. 44–47 ZIF-8 is stable under neutral conditions and can be degraded under an acid tumor microenvironment. Thus, loading ICG and CaO 2 onto ZIF-8 would not only improve the aggregation of ICG, but also enhance the stability of CaO 2 .…”

Thiophene BODIPY-substituted cyclotriphosphazene-derived photosensitizers for photodynamic therapy applications

“…8–12 PSs are generally designed from heteroatom-containing macrocycles, photocages, hybrid materials, organic-fluorophores or metal–organic frameworks. 12–23…”