Co‐Delivery of Precisely Prescribed Multi‐Prodrug Combination by an Engineered Nanocarrier enables Efficient Individualized Cancer Chemotherapy. Issue 12 (14th February 2022)

• Record Type: Journal Article
• Authors: Li, Yuqiang; Jiang, Yitong; Zheng, Ziyan; Du, Nan; Guan, Shuli; Guo, Wenxuan; Tang, Xiaohu; Cui, Jiajunzi; Zhang, Lanqiong; Liu, Kunpeng; Yu, Qingsong; Gan, Zhihua
• Is Part Of: Advanced materials. Volume 34:Issue 12(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-02-14
• Subjects: cancer chemotherapy -- cascade responsivity -- multi‐drug resistance -- ratiometric drug delivery -- synchronized drug release; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adma.202110490
• Languages: English
• ISSNs: 0935-9648

Abstract

Abstract: The limited anticancer drug library and the frequent occurrence of drug resistance have driven monotherapy‐based cancer therapy into a difficult situation. Considering the formidable process of new drug discovery, combination therapy using currently available drugs is a potential alternative. Nevertheless, the barrier between in vitro combination screening and precise in vivo delivery remains insurmountable in the current free‐drug‐ or nanoparticle (NP)‐based combination therapy, which substantially hinders the application of combination therapy. Herein, a novel, precise drug delivery strategy to realize efficient and individualized combination therapy is proposed. Nanomedicine (NM) is engineered using a microfluidics‐based mixer by combining rationally designed polymeric prodrugs of three commercial chemotherapeutics and a cascade‐responsive block copolymer; the NM possesses ratiometric drug loading and synchronized drug release. In addition to quantitative drug loading and precisely controlled drug combination, consistent nanoproperties of these NPs make their in vivo fate predictable. Consequently, tumor growth and metastasis can be effectively inhibited by precisely prescribed NPs derived from in vitro combination screening. This proof‐of‐concept study clearly reveals the feasibility of overcoming the current drug‐library limitations through precise delivery of any predetermined drug combination, facilitating translational research of individualized combination therapy. Abstract : Polymeric prodrug strategy ensures ratiometric loading and synchronized release of in vitro screened drug combinations under the premise of uniform nanoproperty. The scalable nanoparticles made from a pre‐determined prodrug combination and cascade‐responsive vehicle precisely deliver any drug combination into tumor tissue, facilitating the translational research of individualized combination therapy.