A Systematic Strategy of Combinational Blow for Overcoming Cascade Drug Resistance via NIR‐Light‐Triggered Hyperthermia. Issue 20 (8th April 2021)

• Record Type: Journal Article
• Authors: Wang, Lingna; Yu, Yingjie; Wei, Dengshuai; Zhang, Lingpu; Zhang, Xiaoyan; Zhang, Guanxin; Ding, Dan; Xiao, Haihua; Zhang, Deqing
• Is Part Of: Advanced materials. Volume 33:Issue 20(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-04-08
• Subjects: cascade drug resistance -- cisplatin -- combination therapy -- mild hyperthermia -- patient‐derived xenograft models; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adma.202100599
• Languages: English
• ISSNs: 0935-9648

Abstract

Abstract: A systematic combination strategy is proposed for overcoming cisplatin resistance using near‐infrared (NIR)‐light‐triggered hyperthermia. A new photothermal polymer DAP‐F is complexed with a reduction‐sensitive amphiphilic polymer P1 to form F‐NPs with photothermal effect. Subsequently, to build the final nanosystem F–Pt‐NPs, F‐NPs are combined with Pt‐NPs, which are obtained by encapsulating a Pt(IV) prodrug with P1 . Mild hyperthermia (43 °C), generated from F–Pt‐NPs induced by an 808 nm NIR laser, have various effects such as: i) enhancing the cellular membrane permeability to promote the uptake of drugs; ii) activating cisplatin by accelerating the glutathione consumption; iii) increasing the Pt‐DNA adducts formation and possibly the formation of a portion of irreparable Pt‐DNA interstrand crosslinks, thereby inhibiting the repair of DNA. In vitro, it is found that even on cisplatin‐resistant A549DDP cells, the IC50 of F–Pt‐NPs (43 °C) is only 7.0 × 10 −6 m Pt mL −1 . In vivo, on a patient‐derived xenograft model of multidrug resistant lung cancer, the efficacy of the F–Pt‐NPs (43 °C) treatment group shows a tumor inhibition rate of 94%. Taken together, here, an important perspective of resolving cascade drug resistance with the assistance of mild hyperthermia triggered by NIR light is presented, which can be of great significance for clinic translation. Abstract : A new hydrophobic photothermal conjugated polymer, DAP‐F, is synthesized and utilized to prepare a combined nanoparticle system, F–Pt‐nanoparticles (NPs), with a Pt(IV) prodrug. Mild hyperthermia (43 °C), generated from F–Pt‐NPs induced by an 808 nm near‐infrared (NIR) laser, shows potential for clinical translation in therapy of cancer via systematically overcoming the cascade drug resistance (CDR) of cisplatin.