Multifunctional to multistage delivery systems: The evolution of nanoparticles for biomedical applications

Nanomaterials are advancing in several directions with significant progress being achieved with respect to their synthesis, functionalization and biomedical application. In this review, we will describe several classes of prototypical nanocarriers, such as liposomes, silicon particles, and gold nanoshells, in terms of their individual function as well as their synergistic use. Active and passive targeting, photothermal ablation, and drug controlled release constitute some of the crucial functions identified to achieve a medical purpose. Current limitations in targeting, slow clearance, and systemic as well as local toxicity are addressed in reference to the recent studies that attempted to comprehend and solve these issues. The demand for a more sophisticated understanding of the impact of nanomaterials on the body and of their potential immune response underlies this discussion. Combined components are then discussed in the setting of multifunctional nanocarriers, a class of drug delivery systems we envisioned, proposed, and evolved in the last 5 years. In particular, our third generation of nanocarriers, the multistage vectors, usher in the new field of nanomedicine by combining several components onto multifunctional nanocarriers characterized by emerging properties and able to achieve synergistic effects.

[1]  Mauro Ferrari,et al.  Geometrical confinement of gadolinium-based contrast agents in nanoporous particles enhances T1 contrast , 2010, Nature nanotechnology.

[2]  Mauro Ferrari,et al.  E‐Selectin‐Targeted Porous Silicon Particle for Nanoparticle Delivery to the Bone Marrow , 2011, Advanced materials.

[3]  Ho-Chul Shin,et al.  A 3-in-1 polymeric micelle nanocontainer for poorly water-soluble drugs. , 2011, Molecular pharmaceutics.

[4]  Mauro Ferrari,et al.  Nanomedicine—Challenge and Perspectives , 2009 .

[5]  Bernhard Gleich,et al.  Magnetized Aerosols Comprising Superparamagnetic Iron Oxide Nanoparticles Improve Targeted Drug and Gene Delivery to the Lung , 2012, Pharmaceutical Research.

[6]  Wadih Arap,et al.  Combinatorial targeting and nanotechnology applications , 2010, Biomedical microdevices.

[7]  Chun Li,et al.  Near-infrared light triggers release of Paclitaxel from biodegradable microspheres: photothermal effect and enhanced antitumor activity. , 2010, Small.

[8]  Itaru Honma,et al.  Ultrasound‐Triggered Smart Drug Release from a Poly(dimethylsiloxane)– Mesoporous Silica Composite , 2006 .

[9]  Mauro Ferrari,et al.  Mesoporous Silicon‐PLGA Composite Microspheres for the Double Controlled Release of Biomolecules for Orthopedic Tissue Engineering , 2012 .

[10]  Mourad Tighiouart,et al.  HFT-T, a targeting nanoparticle, enhances specific delivery of paclitaxel to folate receptor-positive tumors. , 2009, ACS nano.

[11]  Mauro Ferrari,et al.  Mitotic trafficking of silicon microparticles. , 2009, Nanoscale.

[12]  Michael J. Sailor,et al.  Compatibility of Primary Hepatocytes with Oxidized Nanoporous Silicon , 2001 .

[13]  D. P. O'Neal,et al.  Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. , 2004, Cancer letters.

[14]  Neetu Singh,et al.  Nanoparticles that communicate in vivo to amplify tumour targeting. , 2011, Nature materials.

[15]  Vladimir P Torchilin,et al.  Recent developments in lipid-based pharmaceutical nanocarriers. , 2011, Frontiers in bioscience.

[16]  Joseph M. DeSimone,et al.  Using mechanobiological mimicry of red blood cells to extend circulation times of hydrogel microparticles , 2011, Proceedings of the National Academy of Sciences.

[17]  J. West,et al.  Immunotargeted nanoshells for integrated cancer imaging and therapy. , 2005, Nano letters.

[18]  Mansoor M Amiji,et al.  Multi-functional polymeric nanoparticles for tumour-targeted drug delivery , 2006, Expert opinion on drug delivery.

[19]  Naomi J Halas,et al.  Nanoscale control of near-infrared fluorescence enhancement using Au nanoshells. , 2008, Small.

[20]  Igor Linkov,et al.  Nanotoxicology and nanomedicine: making hard decisions. , 2008, Nanomedicine : nanotechnology, biology, and medicine.

[21]  Mauro Ferrari,et al.  The Transport of Nanoparticles in Blood Vessels: The Effect of Vessel Permeability and Blood Rheology , 2008, Annals of Biomedical Engineering.

[22]  Chung-Yuan Mou,et al.  Mesoporous silica nanoparticles as nanocarriers. , 2011, Chemical communications.

[23]  Benjamin Thierry,et al.  Immunotargeting of Functional Nanoparticles for MRI detection of Apoptotic Tumor Cells , 2009, Advanced materials.

[24]  J. West,et al.  Near-infrared resonant nanoshells for combined optical imaging and photothermal cancer therapy. , 2007, Nano letters.

[25]  Prashant K. Jain,et al.  Plasmonic photothermal therapy (PPTT) using gold nanoparticles , 2008, Lasers in Medical Science.

[26]  Sei-Young Lee,et al.  Shaping nano-/micro-particles for enhanced vascular interaction in laminar flows , 2009, Nanotechnology.

[27]  Mark B. Carter,et al.  The Targeted Delivery of Multicomponent Cargos to Cancer Cells via Nanoporous Particle-Supported Lipid Bilayers , 2011, Nature materials.

[28]  Mauro Ferrari,et al.  Antibiological barrier nanovector technology for cancer applications , 2007, Expert opinion on drug delivery.

[29]  Marcel Warntjes,et al.  Gd2O3 nanoparticles in hematopoietic cells for MRI contrast enhancement , 2011, International Journal of Nanomedicine.

[30]  Wadih Arap,et al.  Networks of gold nanoparticles and bacteriophage as biological sensors and cell-targeting agents , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Mauro Ferrari,et al.  Cellular association and assembly of a multistage delivery system. , 2010, Small.

[32]  Ananth Annapragada,et al.  New Dual Mode Gadolinium Nanoparticle Contrast Agent for Magnetic Resonance Imaging , 2009, PloS one.

[33]  M Ferrari,et al.  Size and shape effects in the biodistribution of intravascularly injected particles. , 2010, Journal of controlled release : official journal of the Controlled Release Society.

[34]  Ronnie H. Fang,et al.  Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform , 2011, Proceedings of the National Academy of Sciences.

[35]  Mauro Ferrari,et al.  The margination propensity of spherical particles for vascular targeting in the microcirculation , 2008, Journal of nanobiotechnology.

[36]  Mauro Ferrari,et al.  Rapid tumoritropic accumulation of systemically injected plateloid particles and their biodistribution. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[37]  T. Xia,et al.  Toxic Potential of Materials at the Nanolevel , 2006, Science.

[38]  R. Bogner,et al.  Application of mesoporous silicon dioxide and silicate in oral amorphous drug delivery systems. , 2012, Journal of pharmaceutical sciences.

[39]  P. Babinec,et al.  In vivo heating of magnetic nanoparticles in alternating magnetic field. , 2004, Medical physics.

[40]  Mauro Ferrari,et al.  Logic-embedded vectors for intracellular partitioning, endosomal escape, and exocytosis of nanoparticles. , 2010, Small.

[41]  Mauro Ferrari,et al.  Near-Infrared Imaging Method for the In Vivo Assessment of the Biodistribution of Nanoporous Silicon Particles , 2011 .

[42]  S. C. Bayliss,et al.  The Culture of Mammalian Cells on Nanostructured Silicon , 1999 .

[43]  Glenn P. Goodrich,et al.  Plasmonic enhancement of molecular fluorescence. , 2007, Nano letters.

[44]  M Ferrari,et al.  The adhesive strength of non-spherical particles mediated by specific interactions. , 2006, Biomaterials.

[45]  Mauro Ferrari,et al.  Agarose Surface Coating Influences Intracellular Accumulation and Enhances Payload Stability of a Nano-delivery System , 2011, Pharmaceutical Research.

[46]  Jennifer Stanfield,et al.  Selective prostate cancer thermal ablation with laser activated gold nanoshells. , 2008, The Journal of urology.

[47]  Wei Lu,et al.  In vitro and in vivo targeting of hollow gold nanoshells directed at epidermal growth factor receptor for photothermal ablation therapy , 2008, Molecular Cancer Therapeutics.

[48]  Mauro Ferrari,et al.  Design of bio-mimetic particles with enhanced vascular interaction. , 2009, Journal of biomechanics.

[49]  Wei Lu,et al.  Targeted Photothermal Ablation of Murine Melanomas with Melanocyte-Stimulating Hormone Analog–Conjugated Hollow Gold Nanospheres , 2009, Clinical Cancer Research.

[50]  Dai Fukumura,et al.  Multistage nanoparticle delivery system for deep penetration into tumor tissue , 2011, Proceedings of the National Academy of Sciences.

[51]  J. West,et al.  Metal Nanoshells , 2005, Annals of Biomedical Engineering.

[52]  B. Sitharaman,et al.  Water-soluble gadofullerenes: toward high-relaxivity, pH-responsive MRI contrast agents. , 2005, Journal of the American Chemical Society.

[53]  Mauro Ferrari,et al.  Tailored porous silicon microparticles: fabrication and properties. , 2010, Chemphyschem : a European journal of chemical physics and physical chemistry.

[54]  Mauro Ferrari,et al.  Nanoparticles for Cancer Detection and Therapy , 2010 .

[55]  M. Ferrari,et al.  In vivo evaluation of safety of nanoporous silicon carriers following single and multiple dose intravenous administrations in mice. , 2010, International journal of pharmaceutics.

[56]  Mauro Ferrari,et al.  Multistage nanovectors: from concept to novel imaging contrast agents and therapeutics. , 2011, Accounts of chemical research.

[57]  Nuria Sanvicens,et al.  Multifunctional nanoparticles--properties and prospects for their use in human medicine. , 2008, Trends in biotechnology.

[58]  P. Choyke,et al.  Clearance properties of nano-sized particles and molecules as imaging agents: considerations and caveats. , 2008, Nanomedicine.

[59]  Mauro Ferrari,et al.  Enabling individualized therapy through nanotechnology. , 2010, Pharmacological research.

[60]  Ira Pastan,et al.  Immunotoxin therapy of cancer. , 1993, Nature reviews. Cancer.

[61]  Anna Moore,et al.  Magnetic Nanoparticles for Cancer Diagnosis and Therapy , 2012, Pharmaceutical Research.

[62]  Darrell J Irvine,et al.  Drug delivery: One nanoparticle, one kill. , 2011, Nature materials.

[63]  R. Stafford,et al.  Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[64]  Hong Yuan,et al.  Receptor-mediated gene delivery by folic acid-modified stearic acid-grafted chitosan micelles , 2011, International journal of nanomedicine.

[65]  Chun Li,et al.  Exceptionally high payload of doxorubicin in hollow gold nanospheres for near-infrared light-triggered drug release. , 2010, ACS nano.

[66]  Thomas D. Dziubla,et al.  PEGylation of nanocarrier drug delivery systems: State of the art , 2008 .

[67]  Mauro Ferrari,et al.  Adhesion of Microfabricated Particles on Vascular Endothelium: A Parametric Analysis , 2004, Annals of Biomedical Engineering.

[68]  Mauro Ferrari,et al.  Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. , 2008, Nature nanotechnology.

[69]  Tammy Y. Olson,et al.  Synthesis, characterization, and tunable optical properties of hollow gold nanospheres. , 2006, The journal of physical chemistry. B.

[70]  Xiaoling Yang,et al.  Ultrasound-triggered smart drug release from multifunctional core-shell capsules one-step fabricated by coaxial electrospray method. , 2011, Langmuir : the ACS journal of surfaces and colloids.

[71]  Thomas F. George,et al.  Modeling nanophotothermal therapy: kinetics of thermal ablation of healthy and cancerous cell organelles and gold nanoparticles. , 2011, Nanomedicine : nanotechnology, biology, and medicine.

[72]  R. Weissleder A clearer vision for in vivo imaging , 2001, Nature Biotechnology.

[73]  Aifei Wang,et al.  pH-Triggered controlled drug release from mesoporous silica nanoparticles via intracelluar dissolution of ZnO nanolids. , 2011, Journal of the American Chemical Society.

[74]  Shiladitya Sengupta,et al.  Temporal targeting of tumour cells and neovasculature with a nanoscale delivery system , 2005, Nature.

[75]  Naomi J Halas,et al.  Fluorescence enhancement by Au nanostructures: nanoshells and nanorods. , 2009, ACS nano.

[76]  S M Moghimi,et al.  Long-circulating and target-specific nanoparticles: theory to practice. , 2001, Pharmacological reviews.

[77]  M Ferrari,et al.  The effect of shape on the margination dynamics of non-neutrally buoyant particles in two-dimensional shear flows. , 2008, Journal of biomechanics.

[78]  Robia G. Pautler,et al.  Nanoshells with Targeted Simultaneous Enhancement of Magnetic and Optical Imaging and Photothermal Therapeutic Response , 2009 .

[79]  Linlin Li,et al.  Mesoporous Silica Nanoparticles: Synthesis, Biocompatibility and Drug Delivery , 2012, Advanced materials.

[80]  Yoo-Hun Suh,et al.  Nanotechnology, nanotoxicology, and neuroscience , 2009, Progress in Neurobiology.

[81]  Naomi J Halas,et al.  Engineered nanomaterials for biophotonics applications: improving sensing, imaging, and therapeutics. , 2003, Annual review of biomedical engineering.

[82]  Mauro Ferrari,et al.  Sustained small interfering RNA delivery by mesoporous silicon particles. , 2010, Cancer research.

[83]  L. Canham,et al.  Derivatized Mesoporous Silicon with Dramatically Improved Stability in Simulated Human Blood Plasma , 1999 .

[84]  L. Canham Bioactive silicon structure fabrication through nanoetching techniques , 1995 .

[85]  Mauro Ferrari,et al.  Cooperative, Nanoparticle‐Enabled Thermal Therapy of Breast Cancer , 2012, Advanced healthcare materials.

[86]  A. Santoro,et al.  Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX/Doxil) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. , 2004, Annals of oncology : official journal of the European Society for Medical Oncology.

[87]  Mauro Ferrari,et al.  Tailoring the degradation kinetics of mesoporous silicon structures through PEGylation. , 2010, Journal of biomedical materials research. Part A.

[88]  Samir Mitragotri,et al.  Red blood cell-mimicking synthetic biomaterial particles , 2009, Proceedings of the National Academy of Sciences.

[89]  Leon Hirsch,et al.  Nanoshell-Enabled Photonics-Based Imaging and Therapy of Cancer , 2004, Technology in cancer research & treatment.