State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
State Key Laboratory of Quality Research in Chinese Medic, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China.
ACS Appl Mater Interfaces. 2021 Apr 7;13(13):14951-14963. doi: 10.1021/acsami.1c00842. Epub 2021 Mar 25.
Synthetic polymersomes have structure similarity to bio-vesicles and could disassemble in response to stimuli for "on-demand" release of encapsulated cargos. Though widely applied as a drug delivery carrier, the burst release mode with structure complete destruction is usually taken for most responsive polymersomes, which would shorten the effective drug reaction time and impair the therapeutic effect. Inspired by the cell organelles' communication mode via regulating membrane permeability for transportation control, we highlight here a biomimetic polymersome with sustained drug release over a specific period of time via near-infrared (NIR) pre-activation. The polymersome is prepared by the self-assembling amphiphilic diblock copolymer (OEGMA--EoS)--PNBOC and encapsulates the hypoxia-activated prodrug AQ4N and upconversion nanoparticle (PEG-UCNP) in its hydrophilic centric cavity. Thirty minutes of NIR pre-activation triggers cross-linking of NBOC and converts the permeability of the polymersome with sustained AQ4N release until 24 h after the NIR pre-activation. The photosensitizer EoS is activated and aggravates environmental hypoxic conditions during a sustained drug release period to boost the AQ4N therapeutic effect. The combination of sustained drug release with concurrent hypoxia intensification results in a highly efficient tumor therapeutic effect both intracellularly and . This biomimetic polymersome will provide an effective and universal tumor therapeutic approach.
合成聚合物囊泡在结构上与生物囊泡相似,可以响应刺激进行“按需”释放囊封货物。尽管被广泛应用于药物传递载体,但大多数响应性聚合物囊泡采用的是结构完全破坏的爆发式释放模式,这会缩短有效药物反应时间并损害治疗效果。受细胞器通过调节膜通透性进行物质运输控制的通讯模式启发,我们通过近红外(NIR)预先激活,突出了一种具有特定时间段内持续药物释放的仿生聚合物囊泡。该聚合物囊泡由两亲性嵌段共聚物(OEGMA-EoS)-PNBOC 自组装而成,并在亲水性中心腔内封装缺氧激活前药 AQ4N 和上转换纳米颗粒(PEG-UCNP)。30 分钟的 NIR 预先激活触发 NBOC 交联,并将聚合物囊泡的通透性转变为持续 AQ4N 释放,直到 NIR 预先激活后 24 小时。光敏剂 EoS 在持续药物释放期间被激活,并加剧环境缺氧条件,以增强 AQ4N 的治疗效果。持续药物释放与同时缺氧加剧相结合,在细胞内和细胞外均产生了高效的肿瘤治疗效果。这种仿生聚合物囊泡将为肿瘤的治疗提供一种有效且通用的方法。