Tumor-Penetrable Nitric Oxide-Releasing Nanoparticles Potentiate Local Antimelanoma Therapy

被引：21

作者：

Lee, Juho ^{[1
]}

Hlaing, Shwe Phyu ^{[1
]}

Hasan, Nurhasni ^{[1
]}

Kwak, Dongmin ^{[1
]}

Kim, Hyunwoo ^{[1
]}

Cao, Jiafu ^{[2
]}

Yoon, In-Soo ^{[1
]}

Yun, Hwayoung ^{[1
]}

Jung, Yunjin ^{[1
]}

Yoo, Jin-Wook ^{[1
]}

机构：

[1] Pusan Natl Univ, Coll Pharm, Busan, South Korea

[2] Guizhou Med Univ, State Key Lab Funct & Applicat Med Plants, Guiyang, Peoples R China

来源：

ACS APPLIED MATERIALS & INTERFACES | 2021年 / 13卷 / 26期

基金：

新加坡国家研究基金会;

关键词：

nitric oxide; nitric oxide releasing nanoparticles; melanoma; local anticancer therapy; tumor penetration; intratumoral injection; EXTRACELLULAR-MATRIX; SURFACE MODIFICATION; DRUG-DELIVERY; CANCER; ALBUMIN; INHIBITION; PARTICLES; DIFFUSION; MELPHALAN; MELANOMA;

D O I：

10.1021/acsami.1c07407

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

Although nitric oxide (NO) has been emerging as a novel local anticancer agent because of its potent cytotoxic effects and lack of off-target side effects, its clinical applications remain a challenge because of the short effective diffusion distance of NO that limits its anticancer activity. In this study, we synthesized albumin-coated poly(lactic-co-glycolic acid) (PLGA)-conjugated linear polyethylenimine diazeniumdiolate (LP/NO) nanoparticles (Alb-PLP/NO NPs) that possess tumor-penetrating and NO-releasing properties for an effective local treatment of melanoma. Sufficient NO-loading and prolonged NO-releasing characteristics of Alb-PLP/NO NPs were acquired through PLGA-conjugated LP/NO copolymer (PLP/NO) synthesis, followed by nanoparticle fabrication. In addition, tumor penetration ability was rendered by the electrostatic adsorption of the albumin on the surface of the nanoparticles. The Alb-PLP/NO NPs showed enhanced intracellular NO delivery efficiency and cytotoxicity to B16F10 murine melanoma cells. In B16F10-tumor-bearing mice, the Alb-PLP/NO NPs showed improved extracellular matrix penetration and spatial distribution in the tumor tissue after intratumoral injection, resulting in enhanced antitumor activity. Taken together, the results suggest that Alb-PLP/NO NPs represent a promising new modality for the local treatment of melanoma.

引用

页码：30383 / 30396

页数：14

共 61 条

[51] Nitric oxide-releasing vehicles for biomedical applications [J].