Ultrasound‐Triggered In Situ Gelation to Overcome Tumor Hypoxia for Enhanced Photodynamic and Sustained Chemotherapy

Abstract

The combination of photodynamic therapy (PDT) and chemotherapy (CT) has promising potential for cancer treatment in overcoming drug resistance and subsequently enhancing the therapeutic efficiency. However, the tumor hypoxia and premature release of drugs as well as off-targeting of the established nanocarrier are still the major challenges. Herein, an ultrasound (US)-triggered in situ hydrogel system is designed to overcome tumor hypoxia and combine PDT and CT (AIPH/PEGDA/DOX/CAT-Ce6). After ultrasonic treatment, the 2,2′-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) will decompose and release a large amount of alkyl radicals, which can activate the crosslink reaction of poly(ethylene glycol) double acrylate (PEGDA) through the amide bond to form the hydrogel structure. This system can achieve the long-term immobilization of CAT-Ce6 and doxorubicin (DOX) at tumor site. Owing to the long-term retention of the hydrogel, the tumor hypoxia can be persistently relieved under the action of CAT and the effect of PDT can be greatly enhanced. Meanwhile, the sustained release of DOX from the hydrogel can achieve the long-term chemotherapy. In vivo experiment demonstrates that the combination of repeatable PDT and sustained chemotherapy based on US-triggered hydrogel system shows a synergistic effect in antitumor therapy without obvious side-effect.

On-Demand Free Radical Release by Laser Irradiation for Photothermal-Thermodynamic Biofilm Inactivation and Tooth Whitening

“…Referring to Figure 3d, XPS analysis reveals that following incubation with AIPH, the percentage of high-valence Mo element (Mo 6+ , binding energy 225 eV) within MB NSs experienced an increase from nearly 0% to 27.6% [42]. Subsequently, we employed 2, 2 -azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as an indicator to further assess the capability of MB NSs for scavenging free radicals [43,44]. As shown in Figure S3, the production of alkyl free radicals was significantly reduced in the presence of MB NSs.…”

Ultrasound Responsive Smart Implantable Hydrogels for Targeted Delivery of Drugs: Reviewing Current Practices

“…It is designed to treat tumor hypoxia by combining photodynamic therapy (PDT) and chemotherapy. 118 After US treatment, the 2.2′-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) decomposes and releases a significant quantity of alkyl free radicals, which can stimulate the crosslinking reaction of PEG double acrylate (PEGDA) via the amide bond, resulting in the hydrogel structure. This system is capable of immobilizing CAT-Ce6 and doxorubicin (DOX) for a long period at the site of the tumor.…”

Controllable Regulation of Ag2S Quantum‐Dot‐Mediated Protein Nanoassemblies for Imaging‐Guided Synergistic PDT/PTT/Chemotherapy against Hypoxic Tumor

“…[11][12][13][14] Considering the existence of high levels of hydrogen peroxide (H 2 O 2 ) inside solid tumors, exploiting catalase (CAT), a specific catalytic enzyme with high efficiency, to decompose H 2 O 2 into oxygen, seems to be an attractive strategy and has been successfully utilized in several types of theranostic nanosystem to relieve tumor hypoxia. [15][16][17] On the other hand, the isoelectric point (PI) of the biocompatible CAT is 5.8-6.4, [18,19] close to the pH of the acidic TME, which may endow it with controllable regulation ability under pathological conditions. Apart from hypoxia, another critical factor in the PDT process is finding the optimal therapeutic time window for light irradiation.…”

“…[24,25] Currently, the development direction of clinical research is moving toward combining PDT with other therapies such as chemotherapy and PTT, which has been confirmed to be more effective than single therapy. [17,[26][27][28] However, the light-activated motif for PDT or PTT encapsulated in conventional nanocarriers may suffer from self-aggregation and premature leakage for in vivo applications, which ultimately affect the therapeutic efficacy. In addition, the hydrophobicity, systemic toxicity, and controllable release of the drugs in chemotherapy are also key challenges existed.…”