Localized Free Radicals Burst Triggered by NIR-II Light for Augmented Low-Temperature Photothermal Therapy

Abstract

As a novel treatment modality of tumors, hypothermal hyperthermia employed relatively lower temperature (<45 °C) to damage cancer cells with mild toxicity to normal tissues. However, beyond that inducible heat resistance of tumor cells, the discounted therapeutic effect of low temperature hyperthermia was also ascribed to poor penetration of exogenous light stimulation and low accumulation of photothermal agents in tumor sites. Herein, we constructed a multifunctional in situ hydrogel of sodium alginate (ALG) via Ca2+ coordinated with ALG to encapsulate the photothermal agent of Ink and azo initiator of 2,2′-azobis­[2-(2-imidazolin-2-yl)­propane]­dihydrochloride (AIPH) for effective tumor treatment. The designed ALG hydrogel was used to improve the therapeutic effect by increased accumulation of Ink and AIPH and avoid potential side-effects caused by the unexpected spread to the surrounding normal tissues. After injection, local low temperature stimulation was generated with near-infrared-II irradiation by a 1064 nm laser, triggering rapid decomposition of AIPH to produce alkyl radicals. The synergistic low temperature photothermal therapy and cytotoxic-free radicals enhanced the apoptosis of tumor cells via physical heat damage and lipid peroxidation. Thus, remarkable inhibition of tumor growth was observed in a subcutaneous colorectal cancer with negligible side effects. Furthermore, the formulation could also exert strong photoacoustic signals, which were utilized to monitor the stability of the composite hydrogel.

Emerging Nanomedicine‐Enabled/Enhanced Nanodynamic Therapies beyond Traditional Photodynamics

“…Photothermal agents of Hu Kaiwen Ink and azo initiator were co-encapsulated into sodium alginate hydrogel for NIR-II-activated lowtemperature photothermal hyperthermia and P-TDT, where the hydrogel was employed for avoiding the undesirable spreading of Ink and azo initiator to the surrounding normal tissues and thus mitigating the potential side effects. [78] This design principle was also realized by the combination of photothermal gold nanorods and azo initiator as encapsulated into the injectable and NIR-responsive hydrogel networks. [79] MW has been utilized in clinic for tumor ablation by microwave thermal therapy (MWTT).…”

Advances and trends of hydrogel therapy platform in localized tumor treatment: A review

“…Localized temperature needs to be high enough to kill cancer cells (over 45°C), 143 which is well above the body temperature (could bring damage to normal cells) and is uncomfortable or even unbearable. Therefore, a low‐temperature (below 45°C) PTT 144 opened up novel routes in cancer therapy (Figure 4). 2, 2′‐azobis[2‐(2‐imidazolin‐2‐yl) propane]‐dihydrochloride/sodium alginate (AIPH/ALG/Ink) hydrogel was triggered by NIR‐II laser light to form low thermal condition, then AIPH generated alkyl radicals to kill tumor cells.…”

“…H&E and TUNEL staining of tumor slicing at the end of treatment. (g) Confocal photos of Calcein‐AM/PI stained HCT116 cells after treatments 145 …”

Solutions to the Drawbacks of Photothermal and Photodynamic Cancer Therapy

“…The article starts with the limitations of phototherapy, summarizes the solutions proposed by researchers in recent years aiming to solve the problems of phototherapy, and provides more comprehensive understanding of phototherapy in antitumor research. The article content includes solutions for thermal damage to normal tissues caused by PTT, [ 34–41 ] solutions for insufficient treatment effect of PTT, solutions for extremely short life and short diffusion distance of ROS in PDT, solutions for lack of oxygen that can produce ROS in PDT, solutions for poor penetration effect of excitation light source, and solutions for insufficient treatment effect of single PDT. Scheme is the sketch map of this topic.…”