Cancer, the uncontrolled growth and spread of malignant cells that can affect almost any tissue of the body, continues to be a major burden to public health. Anticancer chemotherapy is the most important adjuvant therapy, but the targeted and effective therapy to the tumorous tissues or organs, however, remains as a significant challenge in chemotherapy. The proposed work will develop molecular nanofibers of small molecules for controlling the behavior and the fate of cells. The goal of this work is to explore cellular responses to enzyme-instructed formation of molecular nanofibers and eventually develop new nanomedicines to target cancer cells. This application is both hypothesis and design driven. We hypothesize that enzyme- instructed molecular self-assembly, as a unique way to create molecular nanofibers, can modulate extra- and intracellular microenvironment and selectively lead to death of cancer cells. To validate the hypothesis, we will design molecules that self-assemble to form nanofibers upon the action of extra- or intracellular enzyme(s), characterize the physiochemical properties of the nanofibers, and assess the biological properties and effects of the formation of molecular nanofibers in vitro and in vivo. Specifically, this proposed research will (i) design and synthesize substrates that can be converted into molecular nanofibers by enzyme catalysis;(ii) characterize the enzyme-catalyzed reactions of the designed precursors and the behavior and properties of the corresponding molecular nanofibers;(iii) evaluate the activity of the molecular nanofibers against representative cancer cell lines in vitro;and (iv) examine formation and anticancer effects of the molecular nanofibers in vivo using animal models. This research will potentially provide a new platform for creating synthetic nanostructures as nanomedicine to target cancer cells. We anticipate that this new approach will improve fundamental understanding of cancer therapy, provide guiding principles to design anticancer agents at nanoscale, and ultimately lead to a new paradigm of cancer therapy that are based on the integration of molecular self-assembly and enzyme catalysis.

Public Health Relevance

The overall goal of this work is to develop a novel approach for creating nanomedicine to target cancer cells. Using enzyme to instruct the formation of synthetic nanostructures, this approach will ultimately lead to a new paradigm of cancer therapy for improving health and quality of life for the millions of people who will need anticancer treatment in the future.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA142746-02
Application #
8022858
Study Section
Nanotechnology Study Section (NANO)
Program Officer
Forry, Suzanne L
Project Start
2010-02-08
Project End
2015-01-31
Budget Start
2011-02-01
Budget End
2012-01-31
Support Year
2
Fiscal Year
2011
Total Cost
$318,015
Indirect Cost
Name
Brandeis University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
616845814
City
Waltham
State
MA
Country
United States
Zip Code
02454
Li, Jie; Du, Xuewen; Hashim, Saqib et al. (2017) Aromatic-Aromatic Interactions Enable ?-Helix to ?-Sheet Transition of Peptides to Form Supramolecular Hydrogels. J Am Chem Soc 139:71-74
Feng, Zhaoqianqi; Wang, Huaimin; Chen, Xiaoyi et al. (2017) Self-Assembling Ability Determines the Activity of Enzyme-Instructed Self-Assembly for Inhibiting Cancer Cells. J Am Chem Soc 139:15377-15384
Du, Xuewen; Zhou, Jie; Wang, Huainin et al. (2017) In situ generated D-peptidic nanofibrils as multifaceted apoptotic inducers to target cancer cells. Cell Death Dis 8:e2614
Li, Jie; Shi, Junfeng; Medina, Jamie E et al. (2017) Selectively Inducing Cancer Cell Death by Intracellular Enzyme-Instructed Self-Assembly (EISA) of Dipeptide Derivatives. Adv Healthc Mater 6:
Wang, Huaimin; Feng, Zhaoqianqi; Lu, Alvin et al. (2017) Instant Hydrogelation Inspired by Inflammasomes. Angew Chem Int Ed Engl 56:7579-7583
Du, Xuewen; Zhou, Jie; Wang, Jiaqing et al. (2017) Chirality Controls Reaction-Diffusion of Nanoparticles for Inhibiting Cancer Cells. ChemNanoMat 3:17-21
Feng, Zhaoqianqi; Wang, Huaimin; Zhou, Rong et al. (2017) Enzyme-Instructed Assembly and Disassembly Processes for Targeting Downregulation in Cancer Cells. J Am Chem Soc 139:3950-3953
Wang, Huaimin; Feng, Zhaoqianqi; Xu, Bing (2017) Bioinspired assembly of small molecules in cell milieu. Chem Soc Rev 46:2421-2436
Feng, Zhaoqianqi; Zhang, Tengfei; Wang, Huaimin et al. (2017) Supramolecular catalysis and dynamic assemblies for medicine. Chem Soc Rev 46:6470-6479
Zhou, Jie; Li, Jie; Du, Xuewen et al. (2017) Supramolecular biofunctional materials. Biomaterials 129:1-27

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