[Frontiers in Bioscience E4, 529-545, January 1, 2012]

Recent developments in multifunctional hybrid nanoparticles: opportunities and challenges in cancer therapy

Carolina Salvador Morales1, 2, Pedro M. Valencia1, 2 Anjali B. Thakkar1, 2, Edward Swanson1, 2, Robert Langer1,2

1Harvard-MIT Center of Cancer Nanotechnology Excellence, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, 2Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Current multifunctional hybrid nanoparticle platforms
3.1. Multifunctional non-hybrid nanoparticle systems
3.2. Multifunctional hybrid nanoparticles (MHNPs)
3.3. Synthetic strategies of MHNPs
3.4. Stability of MHNPs
3.5. Drug and imaging agent encapsulation of MHNPs
3.5.1. Encapsulation of drug and imaging agents
3.5.2. Controlled release of therapeutic and imaging agents
3.5.3. Drug degradation
4. Medical applications of hybrid nanoparticle platforms
4.1. Introduction to medical applications of MHNPs
4.2. Multidrug resistance: a major challenge to overcome
4.3. Utilizing MHNPs to combat multidrug resistance
4.4. Blood-compatibility of MHNPs
4.4.1. The complement system cascade
4.4.2. The protein binding adsorption phenomenon
4.4.3. Protein binding adsorption on multifunctional hybrid interface
5. Pharmaceutical perspective of MHNPs
5.1. Opportunities and challenges
6. Conclusions and perspectives
7. Acknowledgements
8. References

1. ABSTRACT

Multifunctional hybrid nanoparticles combine some of the unique physical and chemical characteristics of two or more classes of materials, such as polymers, liposomes, metals, quantum dots and mesoporous silica among others, to create a versatile and robust new class of nanoparticles. Here we discuss the most recent synthetic strategies to create these hybrid systems and analyze four key design aspects: stability, encapsulation of therapeutic and imaging agents, controlled release of encapsulated agents, and biocompatibility. Through the combination of multiple nanomaterials, hybrid nanoparticles aim to expand the functionality of single-component systems, using the strengths of one material to improve on weaknesses of another. We then examine how hybrid nanoparticle platforms provide unique opportunities in cancer therapy, specifically in the treatment of multidrug resistant cancer. Finally, we discuss some of the challenges hybrid nanoparticles systems might face in their large scale synthesis and commercialization in the biopharmaceutical industry.