2. Academic Validation
  3. A Tumor Vascular-Targeted Interlocking Trimodal Nanosystem That Induces and Exploits Hypoxia

A Tumor Vascular-Targeted Interlocking Trimodal Nanosystem That Induces and Exploits Hypoxia

  • Adv Sci (Weinh). 2018 May 28;5(8):1800034. doi: 10.1002/advs.201800034.
Xin Luan 1 2 3,  Ying-Yun Guan 1 4,  Hai-Jun Liu 1,  Qin Lu 1,  Mei Zhao 5,  Duxin Sun 2,  Jonathan F Lovell 6,  Peng Sun 7,  Hong-Zhuan Chen 1 3,  Chao Fang 1
Affiliations

Affiliations

  • 1 Hongqiao International Institute of Medicine Shanghai Tongren Hospital and Department of Pharmacology and Chemical Biology Institute of Medical Sciences Shanghai Jiao Tong University School of Medicine (SJTU-SM) 280 South Chongqing Road Shanghai 200025 China.
  • 2 Department of Pharmaceutical Sciences College of Pharmacy University of Michigan Ann Arbor MI 48105 USA.
  • 3 Institute of Interdisciplinary Integrative Biomedical Research Shanghai University of Traditional Chinese Medicine 1200 Cailun Road Shanghai 201210 China.
  • 4 Department of Pharmacy Ruijin Hospital SJTU-SM, 197 Rui Jin Er Road Shanghai 200025 China.
  • 5 Department of Pharmacy Shanghai University of Medicine & Health Sciences 279 Zhouzhu Road Shanghai 201318 China.
  • 6 Department of Biomedical Engineering University at Buffalo State University of New York Buffalo NY 14260 USA.
  • 7 Department of General Surgery Shanghai Tongren Hospital SJTU-SM, 1111 Xianxia Road Shanghai 200336 China.
PMID: 30128230 DOI: 10.1002/advs.201800034
Abstract

Vascular-targeted photodynamic therapy (VTP) is a recently approved strategy for treating solid tumors. However, the exacerbated hypoxic stress makes tumor eradication challenging with such a single modality approach. Here, a new graphene oxide (GO)-based nanosystem for rationally designed, interlocking trimodal Cancer therapy that enables VTP using photosensitizer verteporfin (VP) (1) with codelivery of banoxantrone dihydrochloride (AQ4N) (2), a hypoxia-activated prodrug (HAP), and HIF-1α siRNA (siHIF-1α) (3) is reported. The VTP-induced aggravated hypoxia is highly favorable for AQ4N activation into AQ4 (a Topoisomerase II inhibitor) for chemotherapy. However, the hypoxia-induced HIF-1α acts as a "hidden brake," through downregulating CYP450 (the dominant HAP-activating reductases), to substantially hinder AQ4N activation. siHIF-1α is rationally adopted to suppress the HIF-1α expression upon hypoxia and further enhance AQ4N activation. This trimodal nanosystem significantly delays the growth of PC-3 tumors in vivo compared to the control nanoparticles carrying VP, AQ4N, or siHIF-1α alone or their pairwise combinations. This multimodal nanoparticle design presents, the first example exploiting VTP to actively induce hypoxia for enhanced HAP activation. It is also revealed that HAP activation is still insufficient under hypoxia due to the hidden downregulation of the HAP-activating reductases (CYP450), and this can be well overcome by GO nanoparticle-mediated siHIF-1α intervention.

Keywords

graphene oxide; hypoxia‐activated prodrug; photodynamic therapy; trimodal therapy; tumor hypoxia.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-121649
    拓扑异构酶 II 抑制剂
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z