Subcellular targeting: a new frontier for drug-loaded pharmaceutical nanocarriers and the concept of the magic bullet

被引:44
作者
D'Souza, Gerard G. M. [2 ]
Weissig, Volkmar [1 ]
机构
[1] Midwestern Univ, Coll Pharm Glendale, Glendale, AZ 85308 USA
[2] Massachusetts Coll Pharm & Hlth Sci, Boston, MA 02115 USA
关键词
drug delivery; nanocarriers; subcellular targeting; BLOCK-COPOLYMER MICELLES; FOLATE-RECEPTOR; GENE DELIVERY; IN-VIVO; INTRACELLULAR DELIVERY; ALLOTOPIC EXPRESSION; DNA DELIVERY; LIPOPROTEIN NANOPLATFORM; DQASOME/DNA COMPLEXES; QUANTUM DOTS;
D O I
10.1517/17425240903236101
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The ability of a pharmacologically active molecule selectively to find its target. is closely linked with its potential as a successful therapeutic drug. It has become increasingly evident that there are several pharmacologically active molecules that exert their action on molecular targets inside cell organelles. In the case of a drug molecule with no defined specificity for a particular organelle, the molecule would either need to have sufficiently long metabolic stability to allow for random interaction with the organelle to occur, or a targeting strategy for the intended subcellular compartment would need to be devised in order to potentiate therapeutic effect. In the case of molecules with a stronger affinity for a non-target subcellular compartment, there exists even greater need for the ability to control subcellular disposition. Subcellular or organelle-specific targeting has thus emerged as a new frontier in drug delivery. In this review selected examples of recent work are discussed that the authors believe might eventually lead to the application of pharmaceutical nanocarriers to create the next generation of 'magic bullets' that are capable of delivering a drug payload to a molecular target at a subcellular location.
引用
收藏
页码:1135 / 1148
页数:14
相关论文
共 139 条
[1]   Multi-layered nanoparticles for penetrating the endosome and nuclear membrane via a step-wise membrane fusion process [J].
Akita, Hidetaka ;
Kudo, Asako ;
Minoura, Arisa ;
Yamaguti, Masaya ;
Khalil, Ikrarny A. ;
Moriguchi, Rumiko ;
Masuda, Tomoya ;
Danev, Radostin ;
Nagayama, Kuniaki ;
Kogure, Kentaro ;
Harashima, Hideyoshi .
BIOMATERIALS, 2009, 30 (15) :2940-2949
[2]  
André N, 2000, CANCER RES, V60, P5349
[3]   Paclitaxel targets mitochondria upstream of caspase activation in intact human neuroblastoma cells [J].
André, N ;
Carré, M ;
Brasseur, G ;
Pourroy, B ;
Kovacic, H ;
Briand, C ;
Braguer, D .
FEBS LETTERS, 2002, 532 (1-2) :256-260
[4]  
[Anonymous], ADV COLOUR SCI TECHN
[5]   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 [J].
Bae, Y ;
Nishiyama, N ;
Fukushima, S ;
Koyama, H ;
Yasuhiro, M ;
Kataoka, K .
BIOCONJUGATE CHEMISTRY, 2005, 16 (01) :122-130
[6]   DIFFUSION OF UNIVALENT IONS ACROSS LAMELLAE OF SWOLLEN PHOSPHOLIPIDS [J].
BANGHAM, AD ;
STANDISH, MM ;
WATKINS, JC .
JOURNAL OF MOLECULAR BIOLOGY, 1965, 13 (01) :238-+
[7]   ACTION OF STEROIDS AND STREPTOLYSIN S ON PERMEABILITY OF PHOSPHOLIPID STRUCTURES TO CATIONS [J].
BANGHAM, AD ;
STANDISH, MM ;
WEISSMANN, G .
JOURNAL OF MOLECULAR BIOLOGY, 1965, 13 (01) :253-+
[8]   CATION PERMEABILITY OF PHOSPHOLIPID MODEL MEMBRANES - EFFECT OF NARCOTICS [J].
BANGHAM, AD ;
STANDISH, MM ;
MILLER, N .
NATURE, 1965, 208 (5017) :1295-+
[9]   Endocytic mechanisms for targeted drug delivery [J].
Bareford, Lisa A. ;
Swaan, Peter W. .
ADVANCED DRUG DELIVERY REVIEWS, 2007, 59 (08) :748-758
[10]   Organelle-targeted nanocarriers: Specific delivery of liposomal ceramide to mitochondria enhances its cytotoxicity in vitro and in vivo [J].
Boddapati, Sarathi V. ;
D'Souza, Gerard G. M. ;
Erdogan, Suna ;
Torchilin, Vladimir P. ;
Weissig, Volkmar .
NANO LETTERS, 2008, 8 (08) :2559-2563