Stimuli-responsive clustered nanoparticles for improved tumor penetration and therapeutic efficacy

Hong Jun Li, Jin Zhi Du, Xiao Jiao Du, Cong Fei Xu, Chun Yang Sun, Hong Xia Wang, Zhi Ting Cao, Xian Zhu Yang, Yan Hua Zhu, Shuming Nie, Jun Wang

Research output: Contribution to journalArticlepeer-review


A principal goal of cancer nanomedicine is to deliver therapeutics effectively to cancer cells within solid tumors. However, there are a series of biological barriers that impede nanomedicine from reaching target cells. Here, we report a stimuli-responsive clustered nanoparticle to systematically overcome these multiple barriers by sequentially responding to the endogenous attributes of the tumor microenvironment. The smart polymeric clustered nanoparticle (iCluster) has an initial size of ∼100 nm, which is favorable for long blood circulation and high propensity of extravasation through tumor vascular fenestrations. Once iCluster accumulates at tumor sites, the intrinsic tumor extracellular acidity would trigger the discharge of platinum prodrug-conjugated poly(amidoamine) dendrimers (diameter ∼5 nm). Such a structural alteration greatly facilitates tumor penetration and cell internalization of the therapeutics. The internalized dendrimer prodrugs are further reduced intracellularly to release cisplatin to kill cancer cells. The superior in vivo antitumor activities of iCluster are validated in varying intractable tumor models including poorly permeable pancreatic cancer, drug-resistant cancer, and metastatic cancer, demonstrating its versatility and broad applicability.

Original languageEnglish (US)
Pages (from-to)4164-4169
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number15
StatePublished - Apr 12 2016
Externally publishedYes


  • Nanomedicine
  • Particle size
  • Stimuli responsive
  • Tumor extracellular pH
  • Tumor penetration

ASJC Scopus subject areas

  • General


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