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• W2795693074 endingPage "3736" @default.
• W2795693074 startingPage "3717" @default.
• W2795693074 abstract "A unique asymmetric bow-tie poly(amidoamine) (PAMAM) dendrimer (ABTD) scaffold was designed and developed as a well-defined macromolecular carrier for tumor-targeted drug delivery. The ABTD scaffold in this study consists of a G3-half-dendron (G3-HD) unit and a G1-half-dendron (G1-HD) unit, bearing thiol moiety in each unit and a bis(maleimide) linker unit, which undergo sequential thiol-maleimide coupling to assemble the scaffold. This assembly methodology is applicable to all other combinations of different generations of PAMAM dendrimers. In the prototype ABTD in this study, 16 biotin moieties were tethered to the G3-HD unit and 4 payloads (new-generation taxoid) to the G1-HD via a self-immolative linker to form an ABTD-tumor-targeting conjugate (ABTD-TTC-1). Two other ABTD-TTCs were synthesized, wherein the G1-HD unit was tethered to a fluorescence-labeled taxoid or to a fluorescent probe. These three ABTD-TTCs were constructed by using a common key ABTD 6 bearing a terminal acetylene group in the G1-HD unit, which was fully characterized as a single molecule by high-resolution mass spectrometry and NMR despite its high molecular weight (Mw: 12 876). Then, the click reaction was employed to couple ABTD 6 with a small-molecule payload or fluorescence probe unit bearing a terminal azide moiety. ABTD-TTC-3, as a surrogate of ABTD-TTC-2, showed substantially enhanced internalization into two cancer cell lines via receptor-mediated endocytosis, attributed to multibinding effect. ABTD-TTC-1 exhibited a remarkable selectivity to cancer cells (1400-7500 times) compared to human normal cells, which demonstrates the salient feature and bright prospect of the ABTD-based tumor-targeted drug-delivery system." @default.
• W2795693074 created "2018-04-13" @default.
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• W2795693074 date "2018-04-03" @default.
• W2795693074 modified "2023-10-13" @default.
• W2795693074 title "Design, Synthesis, and Biological Evaluations of Asymmetric Bow-Tie PAMAM Dendrimer-Based Conjugates for Tumor-Targeted Drug Delivery" @default.
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• W2795693074 doi "https://doi.org/10.1021/acsomega.8b00409" @default.
• W2795693074 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5928494" @default.
• W2795693074 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29732446" @default.
• W2795693074 hasPublicationYear "2018" @default.
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