Intratumor Performance and Therapeutic Efficacy of PAMAM Dendrimers Carried by Clustered Nanoparticles

• DOI: 10.1021/acs.nanolett.9b03913
• Publication Date: 2019-11-07T07:32:55Z
• Authors: Hong-Jun Li; Jing Liu; Ying-Li Luo; Sen-Biao Chen; Rong Liu; Jin-Zhi Du; Jun Wang
• Keywords: Pancreatic Neoplasms; Dendrimers; Drug Carriers; Mice; Cell Line, Tumor; Animals; Nanoparticles; Neoplasms, Experimental; 02 engineering and technology; 0210 nano-technology

In recent years, small nanoparticles (NPs) with a diameter of less than 10 nm have aroused considerable interest in biomedical applications. However, their intratumor performance, as well the antitumor efficacy, has not been understood due to size-dependent pharmacokinetics, which presents formidable challenge for delivering comparable amount different NPs tumor tissues. Utilizing multistage delivery strategy, we construct G3-, G5-, and G7-iCluster systems by using poly(amidoamine) (PAMAM) dendrimers generations (G3-, G7-PAMAM) building blocks. The iCluster showed pharmacokinetics similar initial deposition similarity size surface chemistry. After accumulating at site, individual were released, thus, performance was comparatively investigated. Our results indicated that subtle change generation markedly affects activities. G5-iCluster outperformed G3-iCluster treatment efficacy an orthotopic pancreatic model. mechanistic study revealed G3-PAMAM reduced particle retention tissue its weak cell internalization, while G7-PAMAM much penetrative because relatively large strong particle–cell interaction. contrast, G5-PAMAM exhibited balanced penetration, retention. finding highlights huge influence difference performance.