Intracellular targeting of polymer-bound drugs for cancer chemotherapy.
Macromolecules have been traditionally employed as drug carriers due to their ability to selectively accumulate in malignant tissues compared to healthy tissues by either passive or active targeting, thus precluding undesirable side effects generated by free drug. The therapeutic activity proffered by such conjugates requires that the drug concentrate at its specific subcellular target such as the nucleus. Thus, the suitability of macromolecules as carriers also extends to their propensity to deliver the drug to a predetermined intracellular location. As binding a macromolecule to a drug facilitates cellular uptake by endocytosis, various approaches have been employed to either guide the drug to targets different from endosomal/lysosomal compartments by mediating vesicular escape, or to directly accomplish intracellular (cytoplasmic and nuclear) localization. This review discusses the utility of macromolecules in drug delivery and describes the numerous modalities (with a focus on cell-penetrating peptides) currently available for achieving effective intracellular drug delivery.
Nori
Aparna
A
Department of Pharmaceutics and Pharmaceutical Chemistry/CCCD, University of Utah, 30 South, 2000 East, Salt Lake City, UT 84112, USA.
Kopecek
Jindrich
J
D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004337:Drug Carriers; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D015696:Gene Products, tat / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D015497:HIV-1; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D008689:Methacrylates / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D054322:tat Gene Products, Human Immunodeficiency Virus
D004337:Drug Carriers; D015696:Gene Products, tat; D046911:Macromolecular Substances; D008689:Methacrylates; D011108:Polymers; D054322:tat Gene Products, Human Immunodeficiency Virus; C032802:hydroxypropyl methacrylate