A tumor-targeted nanoplatform with stimuli-responsive cascaded activities for multiple model tumor therapy.
Ronghua JinJirong XieXiaoshan YangYu TianPingyun YuanYongkang BaiShiyu LiuBolei CaiXin ChenPublished in: Biomaterials science (2020)
Herein, a rambutan-like nanocomplex (PDA-SNO-GA-HA-DOX, PSGHD for short) was designed to enable effective and accurate tumor therapy. The PSGHD nanocomplex consists of an S-nitrosothiol-functionalized polydopamine (PDA-SNO) core and a gambogic acid-derivatized hyaluronic acid (HA-GA) shell with doxorubicin (DOX) as the cargo. Due to the HA section, the PSGHD nanocomplex can be rapidly and selectively internalized by tumor cells instead of healthy cells in 12 h of co-incubation. After that, the internalized PSGHD nanocomplex is able to gradually release both DOX (agent for chemotherapy) and GA (agent for enhancing thermal damage) under different tumor-specific physiological conditions (low pH and rich HAase). When 808 nm NIR radiation was employed, the PSGHD nanocomplex further demonstrated excellent photothermal conversion to increase the local temperature over 43 °C and convert SNO to nitric oxide (NO, an agent for decreasing drug-efflux). Based on the synergistic effects of NO/DOX and GA/heat, the PSGHD nanocomplex simultaneously achieved tumor-specific low-drug-efflux chemotherapy and low-temperature photothermal therapy, resulting in an eight-fold apoptosis of tumor cells over normal cells under NIR radiation. In vivo data from mouse models further showed that the PSGHD nanocomplex can completely inhibit tumor growth and significantly prolong the survival rate of tumor bearing mice in 50 days, demonstrating the high efficiency of the PSGHD nanocomplex for tumor therapy.
Keyphrases
- pet ct
- cancer therapy
- photodynamic therapy
- nitric oxide
- cell cycle arrest
- hyaluronic acid
- high efficiency
- squamous cell carcinoma
- type diabetes
- room temperature
- cell death
- metabolic syndrome
- machine learning
- gold nanoparticles
- locally advanced
- electronic health record
- radiation therapy
- mouse model
- high resolution
- stem cells
- quantum dots
- endoplasmic reticulum stress
- cell proliferation
- signaling pathway
- data analysis
- smoking cessation
- pi k akt
- high fat diet induced
- nitric oxide synthase
- hydrogen peroxide