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De novo supraparticle construction by a self-assembled Janus cyclopeptide to tame hydrophilic microRNA and hydrophobic molecule for anti-tumor cocktail therapy and augmented immunity
Chemical Engineering Journal ( IF 13.3 ) Pub Date : 2020-06-30 , DOI: 10.1016/j.cej.2020.126080
Junjun She , Yaguang Li , Siqi Yan , Yuwei Yan , Dan Liu , Shichao Li , Yi Guo , Yumeng Xue , Yu Yao , Jin Yan , Wangxiao He

While nanotechnology-assisted cocktail therapy has emerged many advantages in anti-cancer treatment, significant challenges remain as regards efficiently and simultaneously loading two or more drugs with completely different physicochemical properties. The emergence of supramolecule offers an unprecedented opportunity to overcome this pharmaceutical bottleneck. Herein, an engineered Janus cyclopeptide was designed to self-assemble with hydrophilic miR-30C and hydrophobic carnosic acid into a supramolecular nanosphere ~100 nm in diameter termed iNanosphere that possessed excellent dimensional stability and satisfactory resistance against nuclease and peptidase. Moreover, iNanosphere showed an integrin-mediated cellular uptake, followed by GSH-triggered disassemble and release payloads. As expected, iNanosphere in vivo suppressed the xenografted HCT116 colon cancer and allografted MC38 colon cancer, while kept a low therapeutic toxicity and pathological immunogenicity. More importantly, combinations of iNanosphere and anti-PD1 checkpoint blockade therapy resulted in the augmented antitumor response. Collectively, this engineered cyclopeptide reported here will enable us to tame hydrophilic microRNA and hydrophobic molecule for cocktail combination therapy, and such peptide-derived supramolecular nano-architecture demonstrate to be innovative nano-cocktails for superior anti-cancer therapy and hold great potential to be applied in the near future.



中文翻译:

通过自组装的Janus环肽从头构建超微粒,以驯服亲水性microRNA和疏水性分子,用于抗肿瘤鸡尾酒疗法和增强的免疫力

虽然纳米技术辅助鸡尾酒疗法在抗癌治疗中已显示出许多优势,但要有效地同时装载两种或多种具有完全不同的理化性质的药物,仍然存在重大挑战。超分子的出现为克服这一药物瓶颈提供了前所未有的机会。本文中,设计了工程改造的Janus环肽,可与亲水性miR-30C和疏水性肌酸自组装成直径约100 nm的超分子纳米球,称为iNanosphere,它具有出色的尺寸稳定性以及令人满意的抗核酸酶和肽酶抗性。此外,iNanosphere显示出整联蛋白介导的细胞摄取,然后由GSH触发分解并释放有效载荷。不出所料,iNanosphere在体内抑制异种移植的HCT116结肠癌和同种异体移植的MC38结肠癌,同时保持较低的治疗毒性和病理免疫原性。更重要的是,iNanosphere和抗PD1检查点封锁疗法的组合导致抗肿瘤反应增强。总的来说,这里报道的这种工程化的环肽将使我们能够驯服亲水性microRNA和疏水性分子,用于鸡尾酒疗法,这种肽衍生的超分子纳米结构证明是创新的纳米鸡尾酒,具有出色的抗癌治疗作用,并具有很大的潜力。在不久的将来应用。

更新日期:2020-07-03
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