Polymeric photothermal nanoplatform with the inhibition of aquaporin 3 for anti-metastasis therapy of breast cancer

Metastasis, as one of major challenges in the cancer treatment, is responsible for the high mortality of breast cancer. It has been reported that breast cancer cell invasion and metastasis are related to aqua-porin 3 (AQP3), which is the transmembrane transport channel for H2O2 molecules. Moreover, there is agreement that preventing the metastasis of breast tumor cells in combination with inhibiting the tumor growth is a promising strategy for cancer chemotherapy. Herein, we constructed a flexible photothermal crosslinked polymeric nanovehicle for the delivery of the AQP3 inhibitor, [AuCl2(phen)] +Cl- (Auphen). The polymeric nanovehicle (pOMPC-Dex) is comprised of three modules: 1) pOEGMA-co-pMEO2MA serves as the temperature-responsive segment; 2) pCyanineMA acts as the near-infrared (NIR) optical absorb-ing motif for photothermal therapy and is conjugated with pOEGMA-co-pMEO2MA to obtain NIR light stimuli-responsive drug release; and 3) pPBAMA-Dex functions as an acidic tumor microenvironment-responsive unit. Auphen was encapsulated into a nanovehicle (Auphen@pOMPC-Dex) through electrostatic interactions. The designed nanoplatform showed a pH-and NIR light stimuli-responsive drug release pro-file and exhibited the strong inhibition of intracellular H2O2 uptake by breast cancer cells, which led to the inhibition of breast cancer cell migration and invasion in vitro . In a breast cancer mouse model, Auphen@pOMPC-Dex markedly reduced the number of lung metastases in tumor-bearing mice due to the combined suppression of tumor growth and metastasis. Consequently, the fabricated Auphen@pOMPC-Dex may provide a new strategy for the development of comprehensive oncotherapies.Statement of significanceHigh mortality due to metastasis-induced breast cancer has been a key issue that needs to be addressed. It has been reported that aquaporin 3 (AQP3), a transmembrane transport channel for H2O2 molecules was found to have an accelerated effect on breast cancer cell migration. Hence, a flexible crosslinked polymeric nanoplatform with the inhibition of AQP3 was designed to inhibit metastasis of breast can-cer cells. At the same time, we combined suppression of tumor growth with photothermal therapy to enhance the anticancer therapy effect.(c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated summary

Metastasis-induced breast cancer mortality is a critical issue that requires attention. Aquaporin 3 (AQP3), a transmembrane transport channel for H2O2 molecules, has been found to accelerate breast cancer cell migration. Therefore, a flexible crosslinked polymeric nanoplatform with AQP3 inhibition was designed to inhibit the metastasis of breast cancer cells. Additionally, suppression of tumor growth was combined with photothermal therapy to enhance the efficacy of anticancer therapy.