Updated August 2016
Our vision is that by combining basic science understanding with material science, some of the most relevant problems (cancer and other diseases, energy, and environmental issues) of our time will be addressed. In particular, we will focus our initial efforts toward developing nanoparticle-based technologies for biomedical applications.
Listed below are the main research projects we are pursuing:
1. Title: “Multifunctional hybrid nanoparticles as a delivery platform for photodynamic therapy and diagnosis.”
Photodynamic therapy (PDT) has emerged as an alternative approach to chemotherapy and radiotherapy for cancer treatment. The principle of PDT is based on the selective uptake of a photosensitizer (PS) that localizes to a specific tissue/tumor cell type, followed by irradiation with light of the appropriate wavelength to activate the PS. Traditionally, PS molecules (e.g. porphyrins) have dominated the field. Nevertheless, these PS agents have several disadvantages, with low water solubility, poor light absorption, cutaneous photosensitivity, and reduced selectivity for targeted tissues being some of the main drawbacks. Hybrid nanoparticles, composed of both organic and inorganic components, are promising materials for the effective transport of PS. Several advantages can be foreseen by using hybrid nanoparticles as PS delivery systems such as carrying a large payload of PS molecules; in addition, their surface and composition can be tailored to develop multifunctional systems (e.g. target-specific).
Objective: The main goal of this project is to develop multifunctional silica-based hybrid nanoparticles with extraordinary abilities to carry and deliver PS for PDT. We are chemically modifying FDA approved PS to afford stimuli-responsive (pH and redox environment) building blocks. These building units will form the network of the hybrid nanoparticles. We envision that these strategies will afford nanoparticles with maximum payload of PS and improved therapeutic effect.
- Vega, Daniel L.; Lodge, Patrick; and Vivero-Escoto, Juan L.* International Journal of Molecular Sciences (2016), 17 (1), 56.
- Vivero-Escoto, Juan L.* and Elnagheeb, Maram Nanomaterials (2015), 5, 2302-2316.
- “Multifunctional Nanoparticles in Photodynamic Therapy: Recent Developments.” Vivero-Escoto, Juan L.* In Photodynamic Therapy: Fundamentals, Applications and Health Outcomes (2015), Adrian G. Hugo, Nova Science Publisher, Inc. ISBN: 978-1-63463-857-9 (Book chapter, invited).
- Vivero-Escoto, Juan L.* and Vega, Daniel L., RSC Advances (2014), 4, 14400-14407
- Vivero-Escoto, Juan L.*; DeCillis, Daniel; Fritts, Laura; and Vega, Daniel L., Proceedings of SPIE-BIOS (2014), 8931, 89310Z-1/89310Z-10.
Collaborators: Vanderlei Bagnato and Natalia Inada (CEPOF, Physics Institute Sao Carlos, University of Sao Paulo); Kleber Thiago de Oliveira (Chemistry Department, Federal University of Sao Carlos)
Funding: SPRINT FAPESP-UNC Charlotte
2. Title: “Development of Novel Nanoparticle-based Strategies for the Intracellular Delivery of siRNA/DNA of therapeutic proteins”
Nanoparticle-based drug delivery systems (NDDS) carrying therapeutic agents (e.g. nucleic acids and proteins) need to deliver their cargo to the intracellular site of action. Entrapment and degradation of NDDS in endolysosomal compartments are currently considered as major barriers for cytosolic delivery and are, to a large extent, responsible for the low effectiveness of NDDS. Different strategies such as surface functionalization with small targeting molecules or biomolecules are under investigation to enhance the internalization and delivery efficacy of NDDS. Despite some promising results, the ability to enhance delivery of NDDS to the intracellular site of action and control their trajectory within the cell remains elusive.
Objective: The main target of this project is to investigate and control the cellular internalization pathways of surface-modified inorganic nanoparticles with the purpose of enhancing the delivery of siRNA/DNA of therapeutic proteins. Recently we have reported that by chemically functionalizing mesoporous silica nanoparticles (MSN) with cholera or shiga toxin subunit B (CTB/STB), we can influence the internalization pathways (clathrin-mediated endocytosis) of MSN. We are also exploring other functionalization approaches such as the use of poly(ethylenimine) (PEI) or boronic acids.
- Walker, William; Tarannum, Mubin; and Vivero-Escoto, Juan L.* Journal of Materials Chemistry B (2016), 4, 1254-1262.
Collaborators: Kirill Afonin (UNC-Charlotte, Department of Biology); Richard Chi (UNC-Charlotte, Department of Chemistry); Laura Schrum (Carolinas Medical Center)
3. Title: “Hybrid mesoporous silica nanoparticles for target-specific delivery of therapeutic agents for the treatment of cancer”
Nanoparticles are an innovative platform for cancer treatment that reduces systemic toxicity and allows for active targeting of tumor sites to enhance the therapeutic efficacy. Mesoporous silica nanoparticles (MSNs) have emerged as an attractive drug delivery system due to their high surface area, vast functionalization potential, and biocompatibility. The surface of MSNs can be modified with targeting agents that allow not only the specific interaction with cancer cells, but also targeting organelles inside the cells. In addition, active molecules such as photosensitizers and anticancer drugs can be chemically attached or physically loaded into the interior channels of MSNs.
Objective: To demostrate the versatility of mesoporous silica nanoparticles to develop target-specific multifunctional delivery systems for the treatment of cancer. So far, we have shown that by functionalizing MSNs with Cholera toxin subunit B proteins, this material can target the endoplasmic reticulum through a retrograde pathway in cervical cancer cells. Moreover, the modification of the MSN platform with a mucin-1 antibody allowed the accumulation of MSNs in breast cancer tumors in vivo as was demostrated using a genetically engineer mouse model. The therapeutic abilities of the MSN-based drug delivery system were proved by the specific release of anticancer drugs such as cisplatin and gemcitabine in cancer cells over-expressing folate receptors. We are currently working in the functionalization of MSNs with MUC1 antibody for the treatment of pancreatic cancer.
- Dréau, Didier; Jeffords Moore, Laura; Alvarez-Berrios, Merlis P.; Tarannum, Mubin; Mukherjee, Pinku; and Vivero-Escoto, Juan L.* Journal of Biomedical Nanotechnology (2016), accepted ID 16-1271R.
- Alvarez-Berrios, Merlis P. and Vivero-Escoto, Juan L.* International Journal of Nanomedicine (2016), submitted.
Collaborators: Pinku Mukherjee (UNC-Charlotte, Department of Biology); Merlis P. Alvarez-Berrios (Interamerican University of Puerto Rico)
Funding: NCI R15 grant
4. Title: “Design, synthesis and applications of novel photosensitizers for the photodynamic inactivation treatment of multidrug resistance bacteria”
Antibiotics are critical for the treatment of bacterial infections, which have enabled the near eradication of infectious diseases like tuberculosis. However, the overuse of antibiotics has also led to an alarming rise in resistant bacteria that can overcome antibiotics using different mechanisms. As bacteria develop such resistance, infectious from tuberculosis to Escherichia coli (E. coli) may become impossible to treat. Therefore, scientists are racing to find replacements before the life of millions people is threatened due to this issue. Novel alternatives have been recently developed such as photodynamic inactivation. This approach relies on using chemical compounds called photosensitizers to efficiently kill bacteria after illumination with light.
Objective: This project deals with the synthesis of a series of photosensitizer compounds which contain chemical groups that allow them to strongly attach and cause additional damage to E. coli.
Image: Roa Saleh (REU student summer 2016)
Collaborators: Jay Troutman (UNC-Charlotte, Department of Chemistry)
Current support for our research is kindly provided by:
- Charlotte Research Institute
- Wells Fargo
- Oak Ridge Associated Universities