Nanocarriers’ entry into the cell: relevance to drug delivery
Tóm tắt
Nanocarriers offer unique possibilities to overcome cellular barriers in order to improve the delivery of various drugs and drug candidates, including the promising therapeutic biomacromolecules (i.e., nucleic acids, proteins). There are various mechanisms of nanocarrier cell internalization that are dramatically influenced by nanoparticles’ physicochemical properties. Depending on the cellular uptake and intracellular trafficking, different pharmacological applications may be considered. This review will discuss these opportunities, starting with the phagocytosis pathway, which, being increasingly well characterized and understood, has allowed several successes in the treatment of certain cancers and infectious diseases. On the other hand, the non-phagocytic pathways encompass various complicated mechanisms, such as clathrin-mediated endocytosis, caveolae-mediated endocytosis and macropinocytosis, which are more challenging to control for pharmaceutical drug delivery applications. Nevertheless, various strategies are being actively investigated in order to tailor nanocarriers able to deliver anticancer agents, nucleic acids, proteins and peptides for therapeutic applications by these non-phagocytic routes.
Tài liệu tham khảo
Black C, Gregoriadis G (1974) Intracellular fate and effect of liposome-entrapped actinomycin-d injected into rats. Biochem Soc Trans 2:869–871
Couvreur P, Tulkenst P, Roland M, Trouet A, Speiser P (1977) Nanocapsules: a new type of lysosomotropic carrier. FEBS Lett 84:323–326
Peek LJ, Middaugh CR, Berkland C (2008) Nanotechnology in vaccine delivery. Adv Drug Deliv Rev 60:915–928
Aderem A, Underhill D (1999) Mechanisms of phagocytosis in macrophages. Annu Rev Immunol 17:593–623
Rabinovitch M (1995) Professional and nonprofessional phagocytes—an introduction. Trends Cell Biol 5:85–87
Vonarbourg A, Passirani C, Saulnier P, Benoit J (2006) Parameters influencing the stealthiness of colloidal drug delivery systems. Biomaterials 27:4356–4373
Owens D, Peppas N (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307:93–102
Groves E, Dart A, Covarelli V, Caron E (2008) Molecular mechanisms of phagocytic uptake in mammalian cells. Cell Mol Life Sci 65:1957–1976
Vachon E, Martin R, Plumb J, Kwok V, Vandivier R, Glogauer M, Kapus A, Wang X, Chow C, Grinstein S, Downey G (2006) CD44 is a phagocytic receptor. Blood 107:4149–4158
Caron E, Hall A (1998) Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases. Science 282:1717–1721
Swanson JA, Baer SC (1995) Phagocytosis by zippers and triggers. Trends Cell Biol 5:89–93
Claus V, Jahraus A, Tjelle T, Berg T, Kirschke H, Faulstich H, Griffiths G (1998) Lysosomal enzyme trafficking between phagosomes, endosomes, and lysosomes in J774 macrophages. Enrichment of cathepsin H in early endosomes. J Biol Chem 273:9842–9851
Anderson JM, Shive MS (1997) Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev 28:5–24
Lenaerts V, Couvreur P, Christiaens-Leyh D, Joiris E, Roland M, Rollman B, Speiser P (1984) Degradation of poly (isobutyl cyanoacrylate) nanoparticles. Biomaterials 5:65–68
Gregoriadis G (1978) Liposomes in the therapy of lysosomal storage diseases. Nature 275:695–696
Grislain L, Couvreur P, Lenaerts V, Roland M, Deprezdecampeneere D, Speiser P (1983) Pharmacokinetics and distribution of a biodegradable drug-carrier. Int J Pharm 15:335–345
Desjardins M, Griffiths G (2003) Phagocytosis: latex leads the way. Curr Opin Cell Biol 15:498–503
Aderem A (2002) How to eat something bigger than your head. Cell 110:5–8
Korn ED, Weisman RA (1967) Phagocytosis of latex beads by Acanthamoeba. II. Electron microscopic study of the initial events. J Cell Biol 34:219–227
Schäfer V, von Briesen H, Andreesen R, Steffan A, Royer C, Tröster S, Kreuter J, Rübsamen-Waigmann H (1992) Phagocytosis of nanoparticles by human immunodeficiency virus (HlV)-infected macrophages: a possibility for antiviral drug targeting. Pharm Res 9:541–546
Tabata Y, Ikada Y (1988) Effect of the size and surface-charge of polymer microspheres on their phagocytosis by macrophage. Biomaterials 9:356–362
Moghimi SM, Szebeni J (2003) Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. Prog Lipid Res 42:463–478
Heath TD, Lopez NG, Papahadjopoulos D (1985) The effects of liposome size and surface charge on liposome-mediated delivery of methotrexate-gamma-aspartate to cells in vitro. Biochim Biophys Acta 820:74–84
Allen TM, Austin GA, Chonn A, Lin L, Lee KC (1991) Uptake of liposomes by cultured mouse bone marrow macrophages: influence of liposome composition and size. Biochim Biophys Acta Biomembranes 1061:56–64
Vonarbourg A, Passirani C, Saulnier P, Simard P, Leroux JC, Benoit JP (2006) Evaluation of pegylated lipid nanocapsules versus complement system activation and macrophage uptake. J Biomed Mater Res A 78:620–628
Claesson PM, Blomberg E, Fröberg JC, Nylander T, Arnebrant T (1995) Protein interactions at solid surfaces. Adv Colloid Interface Sci 57:161–227
Devine DV, Wong K, Serrano K, Chonn A, Cullis PR (1994) Liposome-complement interactions in rat serum: implications for liposome survival studies. Biochim Biophys Acta 1191:43–51
Chonn A, Cullis PR, Devine DV (1991) The role of surface charge in the activation of the classical and alternative pathways of complement by liposomes. J Immunol 146:4234–4241
Moghimi SM, Muir IS, Illum L, Davis SS, Kolb-Bachofen V (1993) Coating particles with a block co-polymer (poloxamine-908) suppresses opsonization but permits the activity of dysopsonins in the serum. Biochim Biophys Acta 1179:157–165
Scherphof G, Kamps J (1998) Receptor versus non-receptor mediated clearance of liposomes. Adv Drug Deliver Rev 32:81–97
Roser M, Fischer D, Kissel T (1998) Surface-modified biodegradable albumin nano- and microspheres. II: effect of surface charges on in vitro phagocytosis and biodistribution in rats. Eur J Pharm Biopharm 46:255–263
Norman ME, Williams P, Illum L (1992) Human serum albumin as a probe for surface conditioning (opsonization) of block copolymer-coated microspheres. Biomaterials 13:841–849
Leroux J, De Jaeghere F, Anner B, Doelker E, Gurny R (1995) An investigation on the role of plasma and serum opsonins on the evternalization of biodegradable poly(D,L-lactic acid) nanoparticles by human monocytes. Life Sci 57:695–703
Esmaeili F, Ghahremani MH, Esmaeili B, Khoshayand MR, Atyabi F, Dinarvand R (2008) PLGA nanoparticles of different surface properties: preparation and evaluation of their body distribution. Int J Pharm 349:249–255
Bertholon I, Vauthier C, Labarre D (2006) Complement activation by core-shell poly(isobutylcyanoacrylate)-polysaccharide nanoparticles: influences of surface morphology, length, and type of polysaccharide. Pharm Res 23:1313–1323
Jeon S, Lee J, Andrade J, De Gennes P (1991) Protein-surface interactions in the presence of polyethylene oxide: I. Simplified theory. J Colloid Interface Sci 142:149–158
van Oss CJ, Absolom DR, Neumann AW (1980) The “hydrophobic effect”: essentially a van der Waals interaction. Colloid Polym Sci 258:424–427
Gref R, Minamitake Y, Peracchia MT, Trubetskoy V, Torchilin V, Langer R (1994) Biodegradable long-circulating polymeric nanospheres. Science 263:1600–1603
Peracchia MT, Vauthier C, Desmaële D, Gulik A, Dedieu JC, Demoy M, d’Angelo J, Couvreur P (1998) Pegylated nanoparticles from a novel methoxypolyethylene glycol cyanoacrylate-hexadecyl cyanoacrylate amphiphilic copolymer. Pharm Res 15:550–556
Yokoyama M, Miyauchi M, Yamada N, Okano T, Sakurai Y, Kataoka K, Inoue S (1990) Characterization and anticancer activity of the micelle-forming polymeric anticancer drug adriamycin-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer. Cancer Res 50:1693–1700
Couvreur P, Vauthier C (2006) Nanotechnology: intelligent design to treat complex disease. Pharm Res 23:1417–1450
Lemarchand C, Gref R, Couvreur P (2004) Polysaccharide-decorated nanoparticles. Eur J Pharm Biopharm 58:327–341
Raz A, Bucana C, Fogler WE, Poste G, Fidler IJ (1981) Biochemical, morphological, and ultrastructural studies on the uptake of liposomes by murine macrophages. Cancer Res 41:487–494
Schwendener R, Lagocki P, Rahman Y (1984) The effects of charge and size on the interaction of unilamellar liposomes with macrophages. Biochim Biophys Acta Biomembranes 772:93–101
Lee K, Hong K, Papahadjopoulos D (1992) Recognition of liposomes by cells: in vitro binding and endocytosis mediated by specific lipid headgroups and surface charge density. Biochim Biophys Acta Biomembranes 1103:185–197
Rigotti A, Acton SL, Krieger M (1995) The class B scavenger receptors SR-BI and CD36 are receptors for anionic phospholipids. J Biol Chem 270:16221–16224
Derksen JT, Morselt HW, Scherphof GL (1988) Uptake and processing of immunoglobulin-coated liposomes by subpopulations of rat liver macrophages. Biochim Biophys Acta 971:127–136
Betageri GV, Black CD, Szebeni J, Wahl LM, Weinstein JN (1993) Fc-receptor-mediated targeting of antibody-bearing liposomes containing dideoxycytidine triphosphate to human monocyte/macrophages. J Pharm Pharmacol 45:48–53
Kole L, Sarkar K, Mahato SB, Das PK (1994) Neoglycoprotein conjugated liposomes as macrophage specific drug carrier in the therapy of leishmaniasis. Biochem Biophys Res Commun 200:351–358
Yu B, Hailman E, Wright SD (1997) Lipopolysaccharide binding protein and soluble CD14 catalyze exchange of phospholipids. J Clin Invest 99:315–324
Beningo KA, Wang Y (2002) Fc-receptor-mediated phagocytosis is regulated by mechanical properties of the target. J Cell Sci 115:849–856
Sun X, Rossin R, Turner JL, Becker ML, Joralemon MJ, Welch MJ, Wooley KL (2005) An assessment of the effects of shell cross-linked nanoparticle size, core composition, and surface PEGylation on in vivo biodistribution. Biomacromolecules 6:2541–2554
Guo LSS (2001) Amphotericin B colloidal dispersion: an improved antifungal therapy. Adv Drug Deliv Rev 47:149–163
Larabi M, Yardley V, Loiseau PM, Appel M, Legrand P, Gulik A, Bories C, Croft SL, Barratt G (2003) Toxicity and antileishmanial activity of a new stable lipid suspension of amphotericin B. Antimicrob Agents Chemother 47:3774–3779
Drummond CJ, Fong C (1999) Surfactant self-assembly objects as novel drug delivery vehicles. Curr Opin Colloid Interface Sci 4:449–456
Champion JA, Mitragotri S (2006) Role of target geometry in phagocytosis. Proc Natl Acad Sci USA 103:4930–4934
Lenaerts V, Nagelkerke JF, Van Berkel TJ, Couvreur P, Grislain L, Roland M, Speiser P (1984) In vivo uptake of polyisobutyl cyanoacrylate nanoparticles by rat liver Kupffer, endothelial, and parenchymal cells. J Pharm Sci 73:980–982
Chiannilkulchai N, Driouich Z, Benoit JP, Parodi AL, Couvreur P (1989) Doxorubicin-loaded nanoparticles: increased efficiency in murine hepatic metastases. Sel Cancer Ther 5:1–11
Cuvier C, Roblot-Treupel L, Millot JM, Lizard G, Chevillard S, Manfait M, Couvreur P, Poupon MF (1992) Doxorubicin-loaded nanospheres bypass tumor cell multidrug resistance. Biochem Pharmacol 44:509–517
Chiannilkulchai N, Ammoury N, Caillou B, Devissaguet J, Couvreur P (1990) Hepatic tissue distribution of doxorubicin-loaded nanoparticles after i.v. administration in reticulosarcoma M 5076 metastasis-bearing mice. Cancer Chemother Pharmacol 26:122–126
Colin de Verdière A, Dubernet C, Nemati F, Poupon MF, Puisieux F, Couvreur P (1994) Uptake of doxorubicin from loaded nanoparticles in multidrug-resistant leukemic murine cells. Cancer Chemother Pharmacol 33:504–508
de Verdière AC, Dubernet C, Némati F, Soma E, Appel M, Ferté J, Bernard S, Puisieux F, Couvreur P (1997) Reversion of multidrug resistance with polyalkylcyanoacrylate nanoparticles: towards a mechanism of action. Br J Cancer 76:198–205
Kattan J, Droz JP, Couvreur P, Marino JP, Boutan-Laroze A, Rougier P, Brault P, Vranckx H, Grognet JM, Morge X (1992) Phase I clinical trial and pharmacokinetic evaluation of doxorubicin carried by polyisohexylcyanoacrylate nanoparticles. Invest New Drugs 10:191–199
Amselem S, Gabizon A, Barenholz Y (1990) Optimization and upscaling of doxorubicin-containing liposomes for clinical use. J Pharm Sci 79:1045–1052
Gabizon A, Peretz T, Sulkes A, Amselem S, Ben-Yosef R, Ben-Baruch N, Catane R, Biran S, Barenholz Y (1989) Systemic administration of doxorubicin-containing liposomes in cancer patients: a phase I study. Eur J Cancer Clin Oncol 25:1795–1803
Torrado JJ, Espada R, Ballesteros MP, Torrado-Santiago S (2008) Amphotericin B formulations and drug targeting. J Pharm Sci 97:2405–2425
Adler-Moore J, Proffitt RT (2002) AmBisome: liposomal formulation, structure, mechanism of action and pre-clinical experience. J Antimicrob Chemother 49(Suppl 1):21–30
Gaspar R, Préat V, Opperdoes FR, Roland M (1992) Macrophage activation by polymeric nanoparticles of polyalkylcyanoacrylates: activity against intracellular Leishmania donovani associated with hydrogen peroxide production. Pharm Res 9:782–787
Tyagi R, Lala S, Verma AK, Nandy AK, Mahato SB, Maitra A, Basu MK (2005) Targeted delivery of arjunglucoside I using surface hydrophilic and hydrophobic nanocarriers to combat experimental leishmaniasis. J Drug Target 13:161–171
Salem II, Flasher DL, Düzgüneş N (2005) Liposome-encapsulated antibiotics. Methods Enzymol 391:261–291
Fielding RM, Lewis RO, Moon-McDermott L (1998) Altered tissue distribution and elimination of amikacin encapsulated in unilamellar, low-clearance liposomes (MiKasome). Pharm Res 15:1775–1781
Donald PR, Sirgel FA, Venter A, Smit E, Parkin DP, Van de Wal BW, Mitchison DA (2001) The early bactericidal activity of a low-clearance liposomal amikacin in pulmonary tuberculosis. J Antimicrob Chemother 48:877–880
Fattal E, Rojas J, Youssef M, Couvreur P, Andremont A (1991) Liposome-entrapped ampicillin in the treatment of experimental murine listeriosis and salmonellosis. Antimicrob Agents Chemother 35:770–772
Youssef M, Fattal E, Alonso MJ, Roblot-Treupel L, Sauzières J, Tancrède C, Omnès A, Couvreur P, Andremont A (1988) Effectiveness of nanoparticle-bound ampicillin in the treatment of Listeria monocytogenes infection in athymic nude mice. Antimicrob Agents Chemother 32:1204–1207
Bender AR, von Briesen H, Kreuter J, Duncan IB, Rübsamen-Waigmann H (1996) Efficiency of nanoparticles as a carrier system for antiviral agents in human immunodeficiency virus-infected human monocytes/macrophages in vitro. Antimicrob Agents Chemother 40:1467–1471
Löbenberg R, Araujo L, von Briesen H, Rodgers E, Kreuter J (1998) Body distribution of azidothymidine bound to hexyl-cyanoacrylate nanoparticles after i.v. injection to rats. J Control Release 50:21–30
Dembri A, Montisci MJ, Gantier JC, Chacun H, Ponchel G (2001) Targeting of 3′-azido 3′-deoxythymidine (AZT)-loaded poly(isohexylcyanoacrylate) nanospheres to the gastrointestinal mucosa and associated lymphoid tissues. Pharm Res 18:467–473
Hillaireau H, Le Doan T, Appel M, Couvreur P (2006) Hybrid polymer nanocapsules enhance in vitro delivery of azidothymidine-triphosphate to macrophages. J Control Release 116:346–352
Mukherjee S, Ghosh RN, Maxfield FR (1997) Endocytosis. Physiol Rev 77:759–803
Marsh M, Helenius A (2006) Virus entry: open sesame. Cell 124:729–740
Bareford LM, Swaan PW (2007) Endocytic mechanisms for targeted drug delivery. Adv Drug Deliv Rev 59:748–758
Kanaseki T, Kadota K (1969) The “vesicle in a basket”. A morphological study of the coated vesicle isolated from the nerve endings of the guinea pig brain, with special reference to the mechanism of membrane movements. J Cell Biol 42:202–220
Conner SD, Schmid SL (2003) Regulated portals of entry into the cell. Nature 422:37–44
Matter K, Mellman I (1994) Mechanisms of cell polarity: sorting and transport in epithelial cells. Curr Opin Cell Biol 6:545–554
Jones A, Shusta E (2007) Blood–brain barrier transport of therapeutics via receptor-mediation. Pharm Res 24:1759–1771
Strømhaug PE, Berg TO, Gjøen T, Seglen PO (1997) Differences between fluid-phase endocytosis (pinocytosis) and receptor-mediated endocytosis in isolated rat hepatocytes. Eur J Cell Biol 73:28–39
Mayor S, Pagano RE (2007) Pathways of clathrin-independent endocytosis. Nat Rev Mol Cell Biol 8:603–612
Swanson JA, Watts C (1995) Macropinocytosis. Trends Cell Biol 5:424–428
Racoosin EL, Swanson JA (1992) M-CSF-induced macropinocytosis increases solute endocytosis but not receptor-mediated endocytosis in mouse macrophages. J Cell Sci 102:867–880
Zauner W, Farrow NA, Haines AMR (2001) In vitro uptake of polystyrene microspheres: effect of particle size, cell line and cell density. J Control Release 71:39–51
Desai MP, Labhasetwar V, Walter E, Levy RJ, Amidon GL (1997) The mechanism of uptake of biodegradable microparticles in caco-2 cells is size dependent. Pharm Res 14:1568–1573
Desai MP, Labhasetwar V, Amidon GL, Levy RJ (1996) Gastrointestinal uptake of biodegradable microparticles: effect of particle size. Pharm Res 13:1838–1845
Qaddoumi M, Ueda H, Yang J, Davda J, Labhasetwar V, Lee V (2004) The characteristics and mechanisms of uptake of PLGA nanoparticles in rabbit conjunctival epithelial cell layers. Pharm Res 21:641–648
Calvo P, Alonso MJ, Vila-Jato JL, Robinson JR (1996) Improved ocular bioavailability of indomethacin by novel ocular drug carriers. J Pharm Pharmacol 48:1147–1152
Rejman J, Oberle V, Zuhorn IS, Hoekstra D (2004) Size-dependent internalization of particles via the pathways of clathrin- and caveolae-mediated endocytosis. Biochem J 377:159–169
Lai SK, Hida K, Man ST, Chen C, Machamer C, Schroer TA, Hanes J (2007) Privileged delivery of polymer nanoparticles to the perinuclear region of live cells via a non-clathrin, non-degradative pathway. Biomaterials 28:2876–2884
Harush-Frenkel O, Rozentur E, Benita S, Altschuler Y (2008) Surface charge of nanoparticles determines their endocytic and transcytotic pathway in polarized MDCK cells. Biomacromolecules 9:435–443
Mao S, Germershaus O, Fischer D, Linn T, Schnepf R, Kissel T (2005) Uptake and Transport Of PEG-graft-trimethyl-chitosan copolymer-insulin nanocomplexes by epithelial cells. Pharm Res 22:2058–2068
Huang M, Ma Z, Khor E, Lim L (2002) Uptake of FITC-chitosan nanoparticles by A549 cells. Pharm Res 19:1488–1494
Harush-Frenkel O, Debotton N, Benita S, Altschuler Y (2007) Targeting of nanoparticles to the clathrin-mediated endocytic pathway. Biochem Biophys Res Commun 353:26–32
Ropert C, Malvy C, Couvreur P (1993) Inhibition of the Friend retrovirus by antisense oligonucleotides encapsulated in liposomes: mechanism of action. Pharm Res 10:1427–1433
Ellens H, Bentz J, Szoka FC (1984) pH-induced destabilization of phosphatidylethanolamine-containing liposomes: role of bilayer contact. Biochemistry 23:1532–1538
Drummond DC, Zignani M, Leroux J (2000) Current status of pH-sensitive liposomes in drug delivery. Prog Lipid Res 39:409–460
Vasir JK, Labhasetwar V (2007) Biodegradable nanoparticles for cytosolic delivery of therapeutics. Adv Drug Deliv Rev 59:718–728
Straubinger RM, Düzgünes N, Papahadjopoulos D (1985) pH-sensitive liposomes mediate cytoplasmic delivery of encapsulated macromolecules. FEBS Lett 179:148–154
Ropert C, Lavignon M, Dubernet C, Couvreur P, Malvy C (1992) Oligonucleotides encapsulated in pH sensitive liposomes are efficient toward Friend retrovirus. Biochem Biophys Res Commun 183:879–885
Connor J, Norley N, Huang L (1986) Biodistribution of pH-sensitive immunoliposomes. Biochim Biophys Acta 884:474–481
Felgner JH, Kumar R, Sridhar CN, Wheeler CJ, Tsai YJ, Border R, Ramsey P, Martin M, Felgner PL (1994) Enhanced gene delivery and mechanism studies with a novel series of cationic lipid formulations. J Biol Chem 269:2550–2561
Simberg D, Weisman S, Talmon Y, Barenholz Y (2004) DOTAP (and other cationic lipids): chemistry, biophysics, and transfection. Crit Rev Ther Drug Carrier Syst 21:257–317
Demeneix B, Hassani Z, Behr J (2004) Towards multifunctional synthetic vectors. Curr Gene Ther 4:445–455
Boussif O, Lezoualc’h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP (1995) A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc Natl Acad Sci USA 92:7297–7301
Behr JP (1997) The proton sponge: a trick to enter cells the viruses did not exploit. Chimia 51:34–36
Neu M, Fischer D, Kissel T (2005) Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives. J Gene Med 7:992–1009
Behrens I, Pena AIV, Alonso MJ, Kissel T (2002) Comparative uptake studies of bioadhesive and non-bioadhesive nanoparticles in human intestinal cell lines and rats: the effect of mucus on particle adsorption and transport. Pharm Res 19:1185–1193
Bravo-Osuna I, Vauthier C, Farabollini A, Palmieri GF, Ponchel G (2007) Mucoadhesion mechanism of chitosan and thiolated chitosan-poly(isobutyl cyanoacrylate) core-shell nanoparticles. Biomaterials 28:2233–2243
Vila A, Sánchez A, Tobío M, Calvo P, Alonso MJ (2002) Design of biodegradable particles for protein delivery. J Control Release 78:15–24
Calvo P, Vila-Jato JL, Alonso MJ (1997) Evaluation of cationic polymer-coated nanocapsules as ocular drug carriers. Int J Pharm 153:41–50
Brigger I, Morizet J, Aubert G, Chacun H, Terrier-Lacombe M, Couvreur P, Vassal G (2002) Poly(ethylene glycol)-coated hexadecylcyanoacrylate nanospheres display a combined effect for brain tumor targeting. J Pharmacol Exp Ther 303:928–936
Garcia-Garcia E, Gil S, Andrieux K, Desmaële D, Nicolas V, Taran F, Georgin D, Andreux JP, Roux F, Couvreur P (2005) A relevant in vitro rat model for the evaluation of blood-brain barrier translocation of nanoparticles. Cell Mol Life Sci 62:1400–1408
Kim HR, Gil S, Andrieux K, Nicolas V, Appel M, Chacun H, Desmaële D, Taran F, Georgin D, Couvreur P (2007) Low-density lipoprotein receptor-mediated endocytosis of PEGylated nanoparticles in rat brain endothelial cells. Cell Mol Life Sci 64:356–364
Kim HR, Andrieux K, Gil S, Taverna M, Chacun H, Desmaële D, Taran F, Georgin D, Couvreur P (2007) Translocation of poly(ethylene glycol-co-hexadecyl)cyanoacrylate nanoparticles into rat brain endothelial cells: role of apolipoproteins in receptor-mediated endocytosis. Biomacromolecules 8:793–799
Kreuter J (2001) Nanoparticulate systems for brain delivery of drugs. Adv Drug Deliv Rev 47:65–81
Olivier J, Fenart L, Chauvet R, Pariat C, Cecchelli R, Couet W (1999) Indirect evidence that drug brain targeting using polysorbate 80-coated polybutylcyanoacrylate nanoparticles is related to toxicity. Pharm Res 16:1836–1842
Kreuter J, Ramge P, Petrov V, Hamm S, Gelperina SE, Engelhardt B, Alyautdin R, von Briesen H, Begley DJ (2003) Direct evidence that polysorbate-80-coated poly(butylcyanoacrylate) nanoparticles deliver drugs to the CNS via specific mechanisms requiring prior binding of drug to the nanoparticles. Pharm Res 20:409–416
Gillies ER, Goodwin AP, Fréchet JMJ (2004) Acetals as pH-sensitive linkages for drug delivery. Bioconjug Chem 15:1254–1263
Gillies ER, Fréchet JMJ (2005) pH-Responsive copolymer assemblies for controlled release of doxorubicin. Bioconjug Chem 16:361–368
Bae Y, Nishiyama N, Fukushima S, Koyama H, Yasuhiro M, Kataoka K (2005) Preparation and biological characterization of polymeric micelle drug carriers with intracellular pH-triggered drug release property: tumor permeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy. Bioconjug Chem 16:122–130
Chavanpatil MD, Khdair A, Panyam J (2006) Nanoparticles for cellular drug delivery: mechanisms and factors influencing delivery. J Nanosci Nanotechnol 6:2651–2663
Hilgenbrink AR, Low PS (2005) Folate receptor-mediated drug targeting: from therapeutics to diagnostics. J Pharm Sci 94:2135–2146
Weitman SD, Lark RH, Coney LR, Fort DW, Frasca V, Zurawski VR, Kamen BA (1992) Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues. Cancer Res 52:3396–3401
Dauty E, Remy J, Zuber G, Behr J (2002) Intracellular delivery of nanometric DNA particles via the folate receptor. Bioconjug Chem 13:831–839
Sabharanjak S, Mayor S (2004) Folate receptor endocytosis and trafficking. Adv Drug Deliv Rev 56:1099–1109
Stella B, Arpicco S, Peracchia MT, Desmaële D, Hoebeke J, Renoir M, D’Angelo J, Cattel L, Couvreur P (2000) Design of folic acid-conjugated nanoparticles for drug targeting. J Pharm Sci 89:1452–1464
Lee RJ, Low PS (1995) Folate-mediated tumor cell targeting of liposome-entrapped doxorubicin in vitro. Biochim Biophys Acta 1233:134–144
Gabizon A, Shmeeda H, Horowitz AT, Zalipsky S (2004) Tumor cell targeting of liposome-entrapped drugs with phospholipid-anchored folic acid-PEG conjugates. Adv Drug Deliv Rev 56:1177–1192
Kim SH, Jeong JH, Chun KW, Park TG (2005) Target-specific cellular uptake of PLGA nanoparticles coated with poly(L-lysine)-poly(ethylene glycol)-folate conjugate. Langmuir 21:8852–8857
Lee ES, Na K, Bae YH (2005) Doxorubicin loaded pH-sensitive polymeric micelles for reversal of resistant MCF-7 tumor. J Control Release 103:405–418
Qian ZM, Li H, Sun H, Ho K (2002) Targeted drug delivery via the transferrin receptor-mediated endocytosis pathway. Pharmacol Rev 54:561–587
Sahoo SK, Labhasetwar V (2005) Enhanced antiproliferative activity of transferrin-conjugated paclitaxel-loaded nanoparticles is mediated via sustained intracellular drug retention. Mol Pharm 2:373–383
Xu Z, Gu W, Huang J, Sui H, Zhou Z, Yang Y, Yan Z, Li Y (2005) In vitro and in vivo evaluation of actively targetable nanoparticles for paclitaxel delivery. Int J Pharm 288:361–368
Huwyler J, Yang J, Pardridge WM (1997) Receptor mediated delivery of daunomycin using immunoliposomes: pharmacokinetics and tissue distribution in the rat. J Pharmacol Exp Ther 282:1541–1546
Cerletti A, Drewe J, Fricker G, Eberle AN, Huwyler J (2000) Endocytosis and transcytosis of an immunoliposome-based brain drug delivery system. J Drug Target 8:435–446
Lee HJ, Engelhardt B, Lesley J, Bickel U, Pardridge WM (2000) Targeting rat anti-mouse transferrin receptor monoclonal antibodies through blood–brain barrier in mouse. J Pharmacol Exp Ther 292:1048–1052
Maruyama K, Takahashi N, Tagawa T, Nagaike K, Iwatsuru M (1997) Immunoliposomes bearing polyethyleneglycol-coupled Fab’ fragment show prolonged circulation time and high extravasation into targeted solid tumors in vivo. FEBS Lett 413:177–180
Aktaş Y, Yemisci M, Andrieux K, Gürsoy RN, Alonso MJ, Fernandez-Megia E, Novoa-Carballal R, Quiñoá E, Riguera R, Sargon MF, Celik HH, Demir AS, Hincal AA, Dalkara T, Capan Y, Couvreur P (2005) Development and brain delivery of chitosan-PEG nanoparticles functionalized with the monoclonal antibody OX26. Bioconjug Chem 16:1503–1511
Schiffelers RM, Koning GA, ten Hagen TLM, Fens MHAM, Schraa AJ, Janssen APCA, Kok RJ, Molema G, Storm G (2003) Anti-tumor efficacy of tumor vasculature-targeted liposomal doxorubicin. J Control Release 91:115–122
Muro S, Dziubla T, Qiu W, Leferovich J, Cui X, Berk E, Muzykantov VR (2006) Endothelial targeting of high-affinity multivalent polymer nanocarriers directed to intercellular adhesion molecule 1. J Pharmacol Exp Ther 317:1161–1169
Muro S, Wiewrodt R, Thomas A, Koniaris L, Albelda SM, Muzykantov VR, Koval M (2003) A novel endocytic pathway induced by clustering endothelial ICAM-1 or PECAM-1. J Cell Sci 116:1599–1609
Muro S, Schuchman EH, Muzykantov VR (2006) Lysosomal enzyme delivery by ICAM-1-targeted nanocarriers bypassing glycosylation- and clathrin-dependent endocytosis. Mol Ther 13:135–141
Christofidou-Solomidou M, Pietra GG, Solomides CC, Arguiris E, Harshaw D, Fitzgerald GA, Albelda SM, Muzykantov VR (2000) Immunotargeting of glucose oxidase to endothelium in vivo causes oxidative vascular injury in the lungs. Am J Physiol Lung Cell Mol Physiol 278:L794–L805
Torchilin VP (2008) Tat peptide-mediated intracellular delivery of pharmaceutical nanocarriers. Adv Drug Deliv Rev 60:548–558
Lewin M, Carlesso N, Tung CH, Tang XW, Cory D, Scadden DT, Weissleder R (2000) Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat Biotechnol 18:410–414
Yagi N, Yano Y, Hatanaka K, Yokoyama Y, Okuno H (2007) Synthesis and evaluation of a novel lipid-peptide conjugate for functionalized liposome. Bioorg Med Chem Lett 17:2590–2593
Sethuraman VA, Bae YH (2007) TAT peptide-based micelle system for potential active targeting of anti-cancer agents to acidic solid tumors. J Control Release 118:216–224
Kleemann E, Neu M, Jekel N, Fink L, Schmehl T, Gessler T, Seeger W, Kissel T (2005) Nano-carriers for DNA delivery to the lung based upon a TAT-derived peptide covalently coupled to PEG-PEI. J Control Release 109:299–316
Nori A, Jensen KD, Tijerina M, Kopecková P, Kopecek J (2003) Tat-conjugated synthetic macromolecules facilitate cytoplasmic drug delivery to human ovarian carcinoma cells. Bioconjug Chem 14:44–50
Salnikov V, Lukyanenko Y, Frederick C, Lederer W, Lukyanenko V (2007) Probing the outer mitochondrial membrane in cardiac mitochondria with nanoparticles. Biophys J 92:1058–1071
Choi S, Huang P, Jenkins GM, Chan DC, Schiller J, Frohman MA (2006) A common lipid links Mfn-mediated mitochondrial fusion and SNARE-regulated exocytosis. Nat Cell Biol 8:1255–1262
Meeusen S, DeVay R, Block J, Cassidy-Stone A, Wayson S, McCaffery JM, Nunnari J (2006) Mitochondrial inner-membrane fusion and crista maintenance requires the dynamin-related GTPase Mgm1. Cell 127:383–395
Tkachenko AG, Xie H, Coleman D, Glomm W, Ryan J, Anderson MF, Franzen S, Feldheim DL (2003) Multifunctional gold nanoparticle-peptide complexes for nuclear targeting. J Am Chem Soc 125:4700–4701
de la Fuente JM, Berry CC (2005) Tat peptide as an efficient molecule to translocate gold nanoparticles into the cell nucleus. Bioconjug Chem 16:1176–1180
Lee ES, Na K, Bae YH (2005) Super pH-sensitive multifunctional polymeric micelle. Nano Lett 5:325–329
Kale AA, Torchilin VP (2007) Enhanced transfection of tumor cells in vivo using “Smart” pH-sensitive TAT-modified pegylated liposomes. J Drug Target 15:538–545
Devika Chithrani B, Ghazani A, Chan W (2006) Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett 6:662–668
Muro S, Garnacho C, Champion JA, Leferovich J, Gajewski C, Schuchman EH, Mitragotri S, Muzykantov VR (2008) Control of endothelial targeting and intracellular delivery of therapeutic enzymes by modulating the size and shape of ICAM-1-targeted carriers. Mol Ther 16:1450–1458
Gratton SEA, Ropp PA, Pohlhaus PD, Luft JC, Madden VJ, Napier ME, DeSimone JM (2008) The effect of particle design on cellular internalization pathways. Proc Natl Acad Sci USA 105:11613–11618
Gratton SEA, Napier ME, Ropp PA, Tian S, Desimone JM (2008) Microfabricated particles for engineered drug therapies: elucidation into the mechanisms of cellular internalization of print particles. Pharm Res 25:2845–2852
Xu ZP, Niebert M, Porazik K, Walker TL, Cooper HM, Middelberg APJ, Gray PP, Bartlett PF, Lu GQM (2008) Subcellular compartment targeting of layered double hydroxide nanoparticles. J Control Release 130:86–94
Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ (2001) Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol 19:3312–3322
Dvorak HF, Nagy JA, Dvorak JT, Dvorak AM (1988) Identification and characterization of the blood vessels of solid tumors that are leaky to circulating macromolecules. Am J Pathol 133:95–109
Steiniger SC, Kreuter J, Khalansky AS, Skidan IN, Bobruskin AI, Smirnova ZS, Severin SE, Uhl R, Kock M, Geiger KD, Gelperina SE (2004) Chemotherapy of glioblastoma in rats using doxorubicin-loaded nanoparticles. Int J Cancer 109:759–767
Pan XQ, Wang H, Lee RJ (2003) Antitumor activity of folate receptor-targeted liposomal doxorubicin in a KB oral carcinoma murine xenograft model. Pharm Res 20:417–422
Ishida O, Maruyama K, Tanahashi H, Iwatsuru M, Sasaki K, Eriguchi M, Yanagie H (2001) Liposomes bearing polyethyleneglycol-coupled transferrin with intracellular targeting property to the solid tumors in vivo. Pharm Res 18:1042–1048
Nan A, Ghandehari H, Hebert C, Siavash H, Nikitakis N, Reynolds M, Sauk JJ (2005) Water-soluble polymers for targeted drug delivery to human squamous carcinoma of head and neck. J Drug Target 13:189–197
Sapra P, Allen TM (2002) Internalizing antibodies are necessary for improved therapeutic efficacy of antibody-targeted liposomal drugs. Cancer Res 62:7190–7194
Park JW, Kirpotin DB, Hong K, Shalaby R, Shao Y, Nielsen UB, Marks JD, Papahadjopoulos D, Benz CC (2001) Tumor targeting using anti-her2 immunoliposomes. J Control Release 74:95–113
Chen H, Gao J, Lu Y, Kou G, Zhang H, Fan L, Sun Z, Guo Y, Zhong Y (2008) Preparation and characterization of PE38KDEL-loaded anti-HER2 nanoparticles for targeted cancer therapy. J Control Release 128:209–216
Felgner PL, Gadek TR, Holm M, Roman R, Chan HW, Wenz M, Northrop JP, Ringold GM, Danielsen M (1987) Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci USA 84:7413–7417
Dass CR (2004) Lipoplex-mediated delivery of nucleic acids: factors affecting in vivo transfection. J Mol Med 82:579–591
Noone PG, Hohneker KW, Zhou Z, Johnson LG, Foy C, Gipson C, Jones K, Noah TL, Leigh MW, Schwartzbach C, Efthimiou J, Pearlman R, Boucher RC, Knowles MR (2000) Safety and biological efficacy of a lipid-CFTR complex for gene transfer in the nasal epithelium of adult patients with cystic fibrosis. Mol Ther 1:105–114
Stopeck AT, Jones A, Hersh EM, Thompson JA, Finucane DM, Gutheil JC, Gonzalez R (2001) Phase II study of direct intralesional gene transfer of allovectin-7, an HLA-B7/beta2-microglobulin DNA-liposome complex, in patients with metastatic melanoma. Clin Cancer Res 7:2285–2291
Fattal E, Bochot A (2008) State of the art and perspectives for the delivery of antisense oligonucleotides and siRNA by polymeric nanocarriers. Int J Pharm 364:237–248
Dheur S, Dias N, van Aerschot A, Herdewijn P, Bettinger T, Rémy JS, Hélène C, Saison-Behmoaras ET (1999) Polyethylenimine but not cationic lipid improves antisense activity of 3′-capped phosphodiester oligonucleotides. Antisense Nucleic Acid Drug Dev 9:515–525
Grayson AC, Doody A, Putnam D (2006) Biophysical and structural characterization of polyethylenimine-mediated siRNA delivery in vitro. Pharm Res 23:1868–1876
Grzelinski M, Urban-Klein B, Martens T, Lamszus K, Bakowsky U, Höbel S, Czubayko F, Aigner A (2006) RNA interference-mediated gene silencing of pleiotrophin through polyethylenimine-complexed small interfering RNAs in vivo exerts antitumoral effects in glioblastoma xenografts. Hum Gene Ther 17:751–766
Urban-Klein B, Werth S, Abuharbeid S, Czubayko F, Aigner A (2005) RNAi-mediated gene-targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo. Gene Ther 12:461–466
Sidi AA, Ohana P, Benjamin S, Shalev M, Ransom JH, Lamm D, Hochberg A, Leibovitch I (2008) Phase I/II marker lesion study of intravesical BC-819 DNA plasmid in H19 over expressing superficial bladder cancer refractory to bacillus Calmette-Guerin. J Urol 180:2379–2383
Schiffelers RM, Ansari A, Xu J, Zhou Q, Tang Q, Storm G, Molema G, Lu PY, Scaria PV, Woodle MC (2004) Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle. Nucl Acids Res 32:e149
Chavany C, Le Doan T, Couvreur P, Puisieux F, Hélène C (1992) Polyalkylcyanoacrylate nanoparticles as polymeric carriers for antisense oligonucleotides. Pharm Res 9:441–449
Schwab G, Chavany C, Duroux I, Goubin G, Lebeau J, Hélène C, Saison-Behmoaras T (1994) Antisense oligonucleotides adsorbed to polyalkylcyanoacrylate nanoparticles specifically inhibit mutated Ha-ras-mediated cell proliferation and tumorigenicity in nude mice. Proc Natl Acad Sci USA 91:10460–10464
de Martimprey H, Bertrand J, Fusco A, Santoro M, Couvreur P, Vauthier C, Malvy C (2008) siRNA nanoformulation against the Ret/PTC1 junction oncogene is efficient in an in vivo model of papillary thyroid carcinoma. Nucleic Acids Res 36:e2
Fischer D, Bieber T, Li Y, Elsässer HP, Kissel T (1999) A novel non-viral vector for DNA delivery based on low molecular weight, branched polyethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity. Pharm Res 16:1273–1279
Lambert G, Fattal E, Brehier A, Feger J, Couvreur P (1998) Effect of polyisobutylcyanoacrylate nanoparticles and lipofectin loaded with oligonucleotides on cell viability and PKC alpha neosynthesis in HepG2 cells. Biochimie 80:969–976
Lambert G, Fattal E, Pinto-Alphandary H, Gulik A, Couvreur P (2000) Polyisobutylcyanoacrylate nanocapsules containing an aqueous core as a novel colloidal carrier for the delivery of oligonucleotides. Pharm Res 17:707–714
Toub N, Bertrand J, Tamaddon A, Elhamess H, Hillaireau H, Maksimenko A, Maccario J, Malvy C, Fattal E, Couvreur P (2006) Efficacy of siRNA nanocapsules targeted against the EWS-Fli1 oncogene in Ewing sarcoma. Pharm Res 23:892–900
Toub N, Angiari C, Eboué D, Fattal E, Tenu J, Le Doan T, Couvreur P (2005) Cellular fate of oligonucleotides when delivered by nanocapsules of poly(isobutylcyanoacrylate). J Control Release 106:209–213
Lambert G, Bertrand JR, Fattal E, Subra F, Pinto-Alphandary H, Malvy C, Auclair C, Couvreur P (2000) EWS fli-1 antisense nanocapsules inhibits ewing sarcoma-related tumor in mice. Biochem Biophys Res Commun 279:401–406
Woodley JF (1985) Liposomes for oral administration of drugs. Crit Rev Ther Drug Carrier Syst 2:1–18
Aprahamian M, Michel C, Humbert W, Devissaguet JP, Damge C (1987) Transmucosal passage of polyalkylcyanoacrylate nanocapsules as a new drug carrier in the small intestine. Biol Cell 61:69–76
Damgé C, Michel C, Aprahamian M, Couvreur P (1988) New approach for oral administration of insulin with polyalkylcyanoacrylate nanocapsules as drug carrier. Diabetes 37:246–251
Pinto-Alphandary H, Aboubakar M, Jaillard D, Couvreur P, Vauthier C (2003) Visualization of insulin-loaded nanocapsules: in vitro and in vivo studies after oral administration to rats. Pharm Res 20:1071–1084
Damge C, Hillairebuys D, Puech R, Hoeltzel A, Michel C, Ribes G (1995) Effects of orally-administered insulin nanocapsules in normal and diabetic dogs. Diabetes Nutr Metabolism 8:3–9
Tobío M, Sánchez A, Vila A, Soriano I, Evora C, Vila-Jato JL, Alonso MJ (2000) The role of PEG on the stability in digestive fluids and in vivo fate of PEG-PLA nanoparticles following oral administration. Colloids Surf B Biointerfaces 18:315–323
Damgé C, Maincent P, Ubrich N (2007) Oral delivery of insulin associated to polymeric nanoparticles in diabetic rats. J Control Release 117:163–170
Fernández-Urrusuno R, Calvo P, Remuñán-López C, Vila-Jato JL, Alonso MJ (1999) Enhancement of nasal absorption of insulin using chitosan nanoparticles. Pharm Res 16:1576–1581
Vila A, Gill H, McCallion O, Alonso MJ (2004) Transport of PLA-PEG particles across the nasal mucosa: effect of particle size and PEG coating density. J Control Release 98:231–244
Prego C, García M, Torres D, Alonso MJ (2005) Transmucosal macromolecular drug delivery. J Control Release 101:151–162
Sung JC, Pulliam BL, Edwards DA (2007) Nanoparticles for drug delivery to the lungs. Trends Biotechnol 25:563–570
Kawashima Y, Yamamoto H, Takeuchi H, Fujioka S, Hino T (1999) Pulmonary delivery of insulin with nebulized DL-lactide/glycolide copolymer (PLGA) nanospheres to prolong hypoglycemic effect. J Control Release 62:279–287
Zhang Q, Shen Z, Nagai T (2001) Prolonged hypoglycemic effect of insulin-loaded polybutylcyanoacrylate nanoparticles after pulmonary administration to normal rats. Int J Pharm 218:75–80
Yamamoto H, Kuno Y, Sugimoto S, Takeuchi H, Kawashima Y (2005) Surface-modified PLGA nanosphere with chitosan improved pulmonary delivery of calcitonin by mucoadhesion and opening of the intercellular tight junctions. J Control Release 102:373–381
Tsapis N, Bennett D, Jackson B, Weitz DA, Edwards DA (2002) Trojan particles: large porous carriers of nanoparticles for drug delivery. Proc Natl Acad Sci USA 99:12001–12005
Grenha A, Seijo B, Remuñán-López C (2005) Microencapsulated chitosan nanoparticles for lung protein delivery. Eur J Pharm Sci 25:427–437
Grenha A, Grainger CI, Dailey LA, Seijo B, Martin GP, Remuñán-López C, Forbes B (2007) Chitosan nanoparticles are compatible with respiratory epithelial cells in vitro. Eur J Pharm Sci 31:73–84