Boosting O₂^•− Photogeneration via Promoting Intersystem‐Crossing and Electron‐Donating Efficiency of Aza‐BODIPY‐Based Nanoplatforms for Hypoxic‐Tumor Photodynamic Therapy

Abstract

Tumor hypoxia severely impedes the therapeutic efficacy of type II photodynamic therapy (PDT) depending on singlet oxygen (1O2) generation. To combat hypoxic tumors, herein, a new approach is devised to boost superoxide radical (O2•−) photogeneration for type I PDT. Heavy atoms are introduced onto aza‐BODIPY molecules (iodine substituted butoxy‐aza‐BODIPY, IBAB) to promote their intersystem‐crossing (ISC) ability. Meanwhile, methoxy‐poly(ethylene glycol)‐b‐poly(2‐(diisopropylamino) ethyl methacrylate) (mPEG‐PPDA) with enhanced electron‐donating efficiency is employed as a coating matrix to encapsulate IBAB, thereby obtaining amphiphilic aza‐BODIPY nanoplatforms (PPIAB NPs). Under irradiation, triplet‐state IBAB in PPIAB NPs is efficiently generated from singlet state favored by the elevated ISC ability. The electron‐rich environment provided by mPEG‐PPDA can donate triplet‐state IBAB with one electron to form charge‐separated‐state IBAB, which in turn transfers electron to O2 for O2•− production. Significantly, owing to recyclable O2 generated by disproportionation or Harber–Weiss/Fenton reaction, prominent O2•− is generated by PPIAB NPs even in a severe hypoxic environment (2% O2), enabling superior therapeutic efficacy (96.2% tumor‐inhibition rate) over NPs not following this strategy. Thus, the proof‐of‐concept design of ISC‐enhanced and electron‐rich polymer encapsulating PPIAB NPs illuminates the path to preparing O2•− photogenerator for hypoxic cancer treatment.

pH-Responsive Pluronic F127–Lenvatinib-Encapsulated Halogenated Boron-Dipyrromethene Nanoparticles for Combined Photodynamic Therapy and Chemotherapy of Liver Cancer

“…Therefore, detecting the fluorescence of DCF can reflect the level of intracellular ROS. 39 As shown in Figure 4 a, Hep3B cells incubated with LBBr 2 NPs and DCFH-DA only show weak green fluorescence in the control group without laser irradiation, indicating nearly no ROS generation that proved weak dark toxicity of LBBr 2 NPs. However, the bright green fluorescence of DCF could be observed clearly in Hep3B cells under excitation of a 660 nm laser, which was ascribed to the high singlet oxygen quantum yield of BDPBr 2 , reflecting the outstanding ROS generation and phototoxicity of LBBr 2 NPs in Hep3B cells.…”

An All‐Round Athlete on the Track of Phototheranostics: Subtly Regulating the Balance between Radiative and Nonradiative Decays for Multimodal Imaging‐Guided Synergistic Therapy

“…Typically, the integration of intensive electron donor-acceptor (D-A) interaction into the conjugated structured chromophores could remarkably contribute to the bathochromic absorption/ emission and ROS generation on account of the reduced electronic bandgaps and promoted intersystem crossing (ISC) process. [34][35][36][37][38] In this work, as illustrated in Scheme 1, the designed compounds (TI, TSI, and TSSI) comprised by 1,3-bis(dicyanomethylidene)indane moiety (working as A), triphenylamine (TPA) unit (D), and/or thiophene segment (D and π-bridge), showed extremely strong D-A interaction and extended π-conjugation with varying degrees. In this design, TPA moiety is selected because it can not only serve as a strong electronic donor but also act as molecular rotors.…”

Type I Photosensitizers Revitalizing Photodynamic Oncotherapy

“…With the development of supramolecular technology, as shown in Table 1, some supramolecular nanomaterials have also attracted increasing attention for type I PDT. [ 10,11,66 ] For example, Gao et al. devised a O 2 •− photo‐generator (mTHPP‐PDPA) by assembling 5,10,15,20‐tetrakis(meso‐hydroxyphenyl) porphyrin (mTHPP) with electron‐rich polymer poly(ethylene glycol)‐ b ‐poly(2‐(diisopropylamino) ethyl methacrylate) (PEG‐ b ‐PDPA).…”

“…[ 9 ] Nevertheless, most of these photosensitizers are based on type II mechanism in which 1 O 2 is generated to kill cancer cells. [ 10 ] As tumors grow in an exaggerated way, the O 2 ‐supply can hardly meet the metabolic requirements of proliferating tumor cells, leading to the hypoxic tumor microenvironment. [ 3 ] Emerging studies show the rather poor therapeutic efficacy of type II PDT for hypoxic cancer cell killing, owing to the oxygen‐dependent 1 O 2 production.…”