Ultrasound-activated carrier-free nanoprodrugs enhanced universality and efficiency of solid tumor-targeting chemotherapy
The clinical outcome of chemotherapy for solid tumors is significantly restricted by adverse off-target side effects and heterogeneous microenvironments. Herein, we developed a series of ultrasound (US)-activated carrier-free self-assembled nanoprodrugs (PBSN38-OSs) to enhance universality and effic...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2025-08-01
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| Series: | Bioactive Materials |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X25001860 |
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| Summary: | The clinical outcome of chemotherapy for solid tumors is significantly restricted by adverse off-target side effects and heterogeneous microenvironments. Herein, we developed a series of ultrasound (US)-activated carrier-free self-assembled nanoprodrugs (PBSN38-OSs) to enhance universality and efficiency of tumor-targeting chemotherapy. The nanoprodrugs integrated reactive oxygen species (ROS)-responsive pinacol boronic ester-conjugated SN38 (PBSN38) and organic sonosensitizers (OSs). By screening the OSs library, six small molecules with strong binding ability with PBSN38 and high sonodynamic generation efficiency were identified. Then, various PBSN38-OSs nanoprodrugs with high drug-loading content and aqueous stability were fabricated using a facile nano-precipitation method. When exposed to US irradiation, PBSN38-OSs produced extensive ROS in situ, strongly disturbing the endogenous redox balance to overcome the heterogeneity of tumoral ROS content. They subsequently triggered the release of active SN38, thereby resulting in severe oxidative damage and microenvironment-independent cell apoptosis. The antitumor activity and biocompatibility of PBSN38-OSs were thoroughly examined in vitro and in vivo, and two optimal nanoprodrugs were screened, which exhibited potent therapeutical effects toward solid tumor models of colon adenocarcinoma, hepatocellular carcinoma, and pancreatic carcinoma. Overall, the versatile US-activated carrier-free nanoprodrugs could significantly minimize the side effects of chemo-drugs and improve the tumor-targeting chemotherapy efficacy in a spatial-controlled and microenvironment-independent manner, holding great prospects in further clinical translation. |
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| ISSN: | 2452-199X |