Supramolecular chemistry provides tools for the assembly and actuation of molecular systems. The reversibility of association of host-guest systems enables facile assembly and disassembly coupled with 'lock and key'specificity. In our proposed research we will develop new therapeutics based on intracellular host-guest actuation of nanoparticle protherapeutics. This approach provides a new strategy for the creation of bioactive materials that will enable multiple targeting strategies inaccessible with current systems. In our proposed research, we will develop new nanoparticle protherapeutics based on nanoparticle-cucurbituril (CB) host-guest complexes. These complexes dissociate inside the cell in the presence of competitive binders for CB, unmasking and activating the cytotoxic particle therapeutic. This intracellular actuation process will be quantified using mass spectrometric techniques. We will then use the unique intracellular actuation process to enable new targeting approaches, including dual-targeting strategies that are expected to be highly specific to cells overexpressing multiple receptors.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB014277-03
Application #
8616066
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Tucker, Jessica
Project Start
2012-03-01
Project End
2015-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
3
Fiscal Year
2014
Total Cost
$646,521
Indirect Cost
$225,771
Name
University of Massachusetts Amherst
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
153926712
City
Amherst
State
MA
Country
United States
Zip Code
01003
Jeong, Youngdo; Kim, Sung Tae; Jiang, Ying et al. (2016) Nanoparticle-dendrimer hybrid nanocapsules for therapeutic delivery. Nanomedicine (Lond) 11:1571-8
Mizuhara, Tsukasa; Moyano, Daniel F; Rotello, Vincent M (2016) Using the Power of Organic Synthesis for Engineering the Interactions of Nanoparticles with Biological Systems. Nano Today 11:31-40
Huynh, Cong Truc; Nguyen, Minh Khanh; Tonga, Gulen Yesilbag et al. (2016) Photocleavable Hydrogels for Light-Triggered siRNA Release. Adv Healthc Mater 5:305-10
Moyano, Daniel F; Liu, Yuanchang; Peer, Dan et al. (2016) Modulation of Immune Response Using Engineered Nanoparticle Surfaces. Small 12:76-82
Elci, S Gokhan; Yan, Bo; Kim, Sung Tae et al. (2016) Quantitative imaging of 2 nm monolayer-protected gold nanoparticle distributions in tissues using laser ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS). Analyst 141:2418-25
Li, Xiaoning; Yeh, Yi-Cheun; Giri, Karuna et al. (2015) Control of nanoparticle penetration into biofilms through surface design. Chem Commun (Camb) 51:282-5
Mizuhara, Tsukasa; Saha, Krishnendu; Moyano, Daniel F et al. (2015) Acylsulfonamide-Functionalized Zwitterionic Gold Nanoparticles for Enhanced Cellular Uptake at Tumor pH. Angew Chem Int Ed Engl 54:6567-70
Kim, Chang Soo; Mout, Rubul; Zhao, Yunlong et al. (2015) Co-delivery of protein and small molecule therapeutics using nanoparticle-stabilized nanocapsules. Bioconjug Chem 26:950-4
Landis, Ryan F; Tang, Rui; Hou, Singyuk et al. (2015) Zwitterionic Ligands Bound to CdSe/ZnS Quantum Dots Prevent Adhesion to Mammalian Cells. Phosphorus Sulfur Silicon Relat Elem 190:2302-2306
Tonga, Gulen Yesilbag; Jeong, Youngdo; Duncan, Bradley et al. (2015) Supramolecular regulation of bioorthogonal catalysis in cells using nanoparticle-embedded transition metal catalysts. Nat Chem 7:597-603

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