Smart pH-responsive polyhydralazine/bortezomib nanoparticles for remodeling tumor microenvironment and enhancing chemotherapy

被引：35

作者：

Wang, Rui ^{[1
,2
]}

Xu, Xiaodan ^{[3
,4
]}

Li, Dongdong ^{[1
,2
]}

Zhang, Wei ^{[1
,2
]}

Shi, Xueying ^{[1
,2
]}

Xu, Hongxia ^{[1
,2
]}

Hong, Jianqiao ^{[5
]}

Yao, Shasha ^{[1
,2
]}

Liu, Jiwei ^{[1
,2
]}

Wei, Zhenli ^{[6
]}

Piao, Ying ^{[1
,2
]}

Zhou, Zhuxian ^{[1
,2
]}

Shen, Youqing ^{[1
,2
]}

Tang, Jianbin ^{[1
,2
,3
]}

机构：

[1] Zhejiang Univ, Key Lab Biomass Chem Engn, Ctr Bionanoengn, Minist Educ, Hangzhou 310027, Zhejiang, Peoples R China

[2] Zhejiang Univ, Coll Chem & Biol Engn, Hangzhou 310027, Zhejiang, Peoples R China

[3] Zhejiang Univ, ZJU Hangzhou Global Sci & Technol Innovat Ctr, Hangzhou 311215, Peoples R China

[4] Zhejiang Univ, Dept Chem, Hangzhou 310027, Peoples R China

[5] Zhejiang Univ, Affiliated Hosp 2, Dept Orthoped Surg, Sch Med, Hangzhou 310009, Zhejiang, Peoples R China

[6] Zhejiang Univ, Dept Clin Lab, Affiliated Hosp 2, Sch Med, Hangzhou 310009, Zhejiang, Peoples R China

来源：

BIOMATERIALS | 2022年 / 288卷

基金：

中国国家自然科学基金;

关键词：

pH-responsive nanoparticles; Tumor microenvironment modulation; Tumor vessel dilation; Chemo-immunotherapy; IRON-OXIDE NANOPARTICLES; TARGETED DRUG-DELIVERY; CANCER; ACCUMULATION; MODULATION; MECHANISMS; AUTOPHAGY; THERAPY; STROMA;

D O I：

10.1016/j.biomaterials.2022.121737

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

The clinical translation of nanomedicines has been impeded by the unfavorable tumor microenvironment (TME), particularly the tortuous vasculature networks, which significantly influence the transport and distribution of nanomedicines into tumors. In this work, a smart pH-responsive bortezomib (BTZ)-loaded polyhydralazine nanoparticle (PHDZ/BTZ) is presented, which has a great capacity to augment the accumulation of BTZ in tumors by dilating tumor blood vessels via specific release of vasodilator hydralazine (HDZ). The Lewis acid-base co-ordination effect between the boronic bond of BTZ and amino of HDZ empowered PHDZ/BTZ nanoparticles with great stability and high drug loading contents. Once triggered by the acidic tumor environment, HDZ could be released quickly to remodel TME through tumor vessel dilation, hypoxia attenuation, and lead to an increased intratumoral BTZ accumulation. Additionally, our investigation revealed that this pH-responsive nanoparticle dramatically suppressed tumor growth, inhibited the occurrence of lung metastasis with fewer side effects and induced immunogenic cell death (ICD), thereby eliciting immune activation including massive cytotoxic T lymphocytes (CTLs) infiltration in tumors and efficient serum proinflammatory cytokine secretion compared with free BTZ treatment. Thus, with efficient drug loading capacity and potent immune activation, PHDZ nanoparticles exhibit great potential in the delivery of boronic acid-containing drugs aimed at a wide range of diseases.

引用

页数：12

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