Abstract:
: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.
journal_name
Proc Natl Acad Sci U S Aauthors
Li HJ,Du JZ,Du XJ,Xu CF,Sun CY,Wang HX,Cao ZT,Yang XZ,Zhu YH,Nie S,Wang Jdoi
10.1073/pnas.1522080113subject
Has Abstractpub_date
2016-04-12 00:00:00pages
4164-9issue
15eissn
0027-8424issn
1091-6490pii
1522080113journal_volume
113pub_type
杂志文章abstract::Herpesviruses are dsDNA viruses, but their virions may additionally contain RNAs that can be transduced to recipient cells. The biological functions of herpes virion RNA species are unknown. Here we address this issue for EBV, a widespread human herpesvirus with oncogenic potential. We show that EBV-derived particles ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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