Delivered by Publishing Technology to: King's College London IP: 137.73.34.202 On: Thu, 11 Apr 2013 11:03:08 Copyright American Scientific Publishers REVIEW Copyright © 2013 American Scientific Publishers All rights reserved Printed in the United States of America Journal of Nanoscience and Nanotechnology Vol. 13, 2399–2430, 2013 Functionalization of Mesoporous Silica Nanoparticles for Targeting, Biocompatibility, Combined Cancer Therapies and Theragnosis Yaswanth Kuthati 1 , Ping-Jyun Sung 2 , Ching-Feng Weng 1 , Chung-Yuan Mou 3 , and Chia-Hung Lee 1 ∗ 1 Department of Life Science and Institute of Biotechnology, National Dong Hwa University, Hualien 974, Taiwan 2 Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung 944, Taiwan 3 Department of Chemistry, National Taiwan University, Taipei 106, Taiwan The advent of Nanotechnology has paved a way for improved disease treatment strategies, the most noteworthy being the mesoporous silica nanoparticles (MSNs) which have gained much recent attention in the field of cancer therapy and its diagnosis. The flaws of the current-day strategies can be overcome by this superior technology through its targeting ability in delivering drugs and image able agents specifically to the tumor sites. MSNs have unique biocompatibility features, its high surface area which contributes in large amount of drug loading and its facility to monitor size and shape of the nanoparticles are few of the positives which makes this technology an enormous asset for the field of Nanotechnology. This review paper is structured in such a way wherein we initially have discussed about the synthesis methods and various functionalization approaches for MSN followed by the different methods used for targeting cancer cells and the latest advances in controlled drug release. Some of the highlights of this review are the biocompatibility of MSNs, in vivo results of MSNs on cancer therapy. This review paper also shortly discuss about combined cancer therapies to overcome the challenges in current-day cancer treatment. Finally, we converge briefly on the recent advancements in the use of hybrid MSNs for obtaining multiple functions. Keywords: Mesoporous Silica, Nanoparticles, Biocompatibility, Targeting, Theragnosis, Combined Therapies. CONTENTS 1. An Introduction to Mesoporous Silica: Synthesis and Functionalization .................................... 2401 1.1. Co-Condensation ................................ 2401 1.2. Grafting (Post-Synthetic Modification) ................ 2401 2. Targeting Strategies and the Recent Advances in Targeting Cancer Cells Using Mesoporous Silica Nanoparticles as Carriers .............................. 2402 2.1. Passive Targeting ................................ 2402 2.2. Active Targeting ................................. 2403 3. Stimuli Responsive Controlled Drug Release Using Mesoporous Silica Nanoparticles ........................ 2407 3.1. pH Responsive Drug Delivery Systems ............... 2408 3.2. Light and Magnetic Controlled Drug Release .......... 2409 3.3. Enzymatic and Thermo Responsive Drug Release ....... 2410 3.4. Dual Responsive Drug Release ..................... 2411 4. Mesoporous Silica Nanoparticles Biocompatibility, Bio-Distribution and Particle Clearance Mechanisms ........ 2412 ∗ Author to whom correspondence should be addressed. 4.1. Effect of MSN Shape ............................. 2412 4.2. Effect of Size and Porosity ........................ 2413 4.3. Effect of Surface Functionalization and Charge ......... 2415 4.4. Effect of Particle Synthesis and Surface Coating ........ 2417 4.5. Effect of Administration Route ..................... 2418 5. Combined Cancer Therapies ........................... 2419 5.1. siRNA and Chemotherapeutic Drug Co-Delivery ........ 2419 5.2. Combined Photodynamic Therapy and Chemotherapy ........................ 2419 5.3. Combined Photothermal Therapy and Chemotherapy ........................ 2419 5.4. Chemotherapy and/or Hyperthermia Depending on the Requirement ..................... 2420 5.5. Cocktail Drug Therapy ........................... 2421 6. Multifunctional Hybrid Mesoporous Silica Nanoparticles for Theragnosis and Targeted Drug Delivery .................. 2421 6.1. Hybrid Nano Composites with Silica Shell ............ 2422 7. Future Perspective ................................... 2424 Acknowledgment .................................... 2425 References and Notes ................................ 2425 J. Nanosci. Nanotechnol. 2013, Vol. 13, No. 4 1533-4880/2013/13/2399/032 doi:10.1166/jnn.2013.7363 2399