Highly Efficient Far‐Red/NIR‐Absorbing Neutral Ir(III) Complex Micelles for Potent Photodynamic/Photothermal Therapy

Abstract

A critical issue in photodynamic therapy (PDT) is inadequate reactive oxygen species (ROS) generation in tumors, causing inevitable survival of tumor cells that usually results in tumor recurrence and metastasis. Existing photosensitizers frequently suffer from relatively low light‐to‐ROS conversion efficiency with far‐red/near‐infrared (NIR) light excitation due to low‐lying excited states that lead to rapid non‐radiative decays. Here, a neutral Ir(III) complex bearing distyryl boron dipyrromethene (BODIPY‐Ir) is reported to efficiently produce both ROS and hyperthermia upon far‐red light activation for potentiating in vivo tumor suppression through micellization of BODIPY‐Ir to form “Micelle‐Ir”. BODIPY‐Ir absorbs strongly at 550–750 nm with a band maximum at 685 nm, and possesses a long‐lived triplet excited state with sufficient non‐radiative decays. Upon micellization, BODIPY‐Ir forms J‐type aggregates within Micelle‐Ir, which boosts both singlet oxygen generation and the photothermal effect through the high molar extinction coefficient and amplification of light‐to‐ROS/heat conversion, causing severe cell apoptosis. Bifunctional Micelle‐Ir that accumulates in tumors completely destroys orthotopic 4T1 breast tumors via synergistic PDT/photothermal therapy (PTT) damage under light irradiation, and enables remarkable suppression of metastatic nodules in the lungs, together without significant dark cytotoxicity. The present study offers an emerging approach to develop far‐red/NIR photosensitizers toward potent cancer therapy.

Progress of Nanomaterials in Photodynamic Therapy Against Tumor

“…Furthermore, some multifunctional nanomaterials can increase the levels of O 2 and ROS in tissues by mediating photocatalytic oxygen production and Fenton reaction. In addition, upconverting NPs can enhance light delivery in tumor tissues by converting more penetrating NIR to visible light or preparing them as persistent luminescent NPs ( Liu B. et al, 2021 ). In addition to enhancing PSs in tumor tissues through physicochemically optimized passive targeting, ligand-modified active targeting, and stimulus-responsive release.…”

Theranostic Nanoplatform with Sequential SDT and ADV Effects in Response to Well-Programmed LIFU Irradiation for Cervical Cancer

“…85-23, revised 1996). To construct HeLa tumor xenografts, 1×10 6 HeLa cells suspended in 100 µL of PBS solution were subcutaneously injected into the right side of each nude mouse.…”

“…Photodynamic therapy (PDT) and photothermal therapy (PTT) have been extensively studied for minimally invasive tumor treatment. [5][6][7] However, since the penetration depth of light waves into the human body is less than 10 mm, 8 these methods have only certain effects on superficial tumors, which limit their effects to treat cervical cancer and its metastases at different FIGO stages. In addition, nanomedicines for PDT or PTT cannot penetrate deep into the tumor.…”

A Bacteria‐Responsive Porphyrin for Adaptable Photodynamic/Photothermal Therapy

“…Owing to large extinction coefficients, porphyrins and their derivatives have been extensively applied for fluorescence imaging, photodynamic therapy (PDT), as well as photothermal therapy (PTT) [3–10] . Porphyrin‐based PTT and PDT are non‐contact, convenient, and effective therapeutic methods with low risk in generating drug resistance, and have been applied in clinical treatments for bacterial infections [11–28] . In general, porphyrin derivatives with heavy atoms, cations, and appropriate substituents are commonly used in antimicrobial PDT owing to their high yield of reactive oxygen species, good affinity with bacterial membranes, and non‐stacking properties [29–32] .…”

“…[3][4][5][6][7][8][9][10] Porphyrin-based PTT and PDT are non-contact, convenient, and effective therapeutic methods with low risk in generating drug resistance, and have been applied in clinical treatments for bacterial infections. [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] In general, porphyrin derivatives with heavy atoms, cations, and appropriate substituents are commonly used in antimicrobial PDT owing to their high yield of reactive oxygen species, good affinity with bacterial membranes, and non-stacking properties. [29][30][31][32] While for PTT treatments, porphyrin derivatives with changed π electrons, larger conjugated structures, and aggregated morphologies are usually designed because of their red-shifted absorption and high non-radiative decay efficiency.…”