An effective NIR laser/tumor-microenvironment co-responsive cancer theranostic nanoplatform with multi-modal imaging and therapies. Issue 24 (11th June 2021)

• Record Type: Journal Article
• Authors: Cheng, Hanlong; Wang, Xueyan; Liu, Xuan; Wang, Xin; Wen, Hao; Cheng, Yinkai; Xie, Anjian; Shen, Yuhua; Tang, Rupei; Zhu, Manzhou
• Is Part Of: Nanoscale. Volume 13:Issue 24(2021)
• Page Start: 10816
• Page End: 10828
• Publication Date: 2021-06-11
• Subjects: Nanoscience -- Periodicals; Nanotechnology -- Periodicals; 620.505
• DOI: 10.1039/d1nr01645h
• Languages: English
• ISSNs: 2040-3364

Abstract

Abstract : An effective cancer therapeutic nanoplatform with multi-modal imaging and synergistic photothermal/photodynamic therapy/ferroptosis. Abstract : Cancer is still a major threat to human health at present. Developing new types of integrated nanoplatforms for the accurate diagnosis and effective treatment of cancer is very significant. Herein, an intelligent dual-stage core–shell cancer theranostic nanoplatform (Fe 3+ @Au1Ag24@PbP) with NIR laser/tumor-microenvironment (TME) co-responsiveness and multi-modal imaging-therapy was successfully prepared, which was composed of the precisely structured oil-soluble Au1Ag24 nanoclusters (NCs) and Fe 3+ ions easily assembled within the oil and aqueous phases of the polyethylene glycol (PEG) block grafted polyketal (PK) copolymer (PK- b -PEG, PbP) vesicles, respectively. In this system, we were delighted to find that the prepared Au1Ag24 NCs possess multi-photoresponsive properties, endowing the nanoplatform with photoacoustic (PA)/photothermal (PT) imaging and synergetic photothermal therapy (PTT)/photodynamic therapy (PDT) for cancer under near-infrared (NIR) laser irradiation. On the other hand, Fe 3+ ions exhibit multi-TME response and regulation behaviors, including as catalysts for the decomposition of endogenous hydrogen peroxide (H2 O2 ) in the solid tumor to produce O2 and as the oxidizing agent for the consumption of the intracellular GSH to avoid the reduction of the generated 1 O2 ; therefore, the synchronously formed Fe 2+ ions from the redox of Fe 3+ with GSH could further react with H2 O2 to produce hydroxyl radical (˙OH), which induced ferroptosis-based cancer treatment. The PbP shell possesses TME/pH sensitivity for controlled drug release and passive targeting, causing a large increase in Au1Ag24/Fe 3+ accumulation within the weakly acidic tumor region and reducing the side effects on normal tissues. Both in vitro and in vivo experiments demonstrate that the Fe 3+ @Au1Ag24@PbP nanoplatform presented excellent PA/PT imaging-guided synergetic PTT/PDT/ferroptosis effects toward tumor cells and tumors. This integrating multi-responsive and multi-modal theranostic nanoplatform paves a new way for effective cancer therapy.