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 aquaporin 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 absorbing 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 profile 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 SIGNIFICANCE: High 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 cancer cells. At the same time, we combined suppression of tumor growth with photothermal therapy to enhance the anticancer therapy effect.

A Biomimetic Nonantibiotic Nanoplatform for Low-Temperature Photothermal Treatment of Urinary Tract Infections Caused by Uropathogenic Escherichia coli.

Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) remain a matter of concern, as the clinical use of multiple antibiotics induces antibiotic resistance in bacteria, resulting in the failure of treatments. Despite the emergence of anti-adhesion strategies that can prevent the development of bacterial drug resistance, these strategies are mainly used for disease prevention rather than effective treatment. Photothermal therapy (PTT) has emerged as an efficient alternative for the elimination of bacteria. Nevertheless, high local temperatures related to PTT probably cause damage to surrounding healthy tissue. Herein, a biomimetic nonantibiotic nanoplatform for low-temperature photothermal treatment of UTIs is developed. The nanoplatform comprises polydopamine (PDA) photothermal core and biphenyl mannoside (Man) shell with multivalent high-affinity to UPEC. Scanning electron microscope (SEM) shows PDA-Man possessed ultra-strong targeting binding ability toward UPEC. It is the fact that this impulse UPEC to form a large bacterial cluster. Consequently, the high photothermal energy of the PDA-Man appears predominantly in the affected bacterial area, while the overall environment remains at a low temperature. The fabricated nanoplatform shows excellent photothermal bactericidal effects, approximately 100% in a UTI model. Overall, this low-temperature photothermal nanoplatform provides an appropriate strategy for the elimination of bacteria in clinical applications.