title: Insight into nanoparticle cellular uptake and intracellular targeting.
abstract: Collaborative efforts from the fields of biology, materials science, and engineering are leading to exciting progress in the development of nanomedicines. Since the targets of many therapeutic agents are localized in subcellular compartments, modulation of nanoparticle-cell interactions for efficient cellular uptake through the plasma membrane and the development of nanomedicines for precise delivery to subcellular compartments remain formidable challenges. Cellular internalization routes determine the post-internalization fate and intracellular localization of nanoparticles. This review highlights the cellular uptake routes most relevant to the field of non-targeted nanomedicine and presents an account of ligand-targeted nanoparticles for receptor-mediated cellular internalization as a strategy for modulating the cellular uptake of nanoparticles. Ligand-targeted nanoparticles have been the main impetus behind the progress of nanomedicines towards the clinic. This strategy has already resulted in remarkable progress towards effective oral delivery of nanomedicines that can overcome the intestinal epithelial barrier. A detailed overview of the recent developments in subcellular targeting as a novel platform for next-generation organelle-specific nanomedicines is also provided. Each section of the review includes prospects, potential, and concrete expectations from the field of targeted nanomedicines and strategies to meet those expectations.
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA.
authors.forename: Basit
authors.initials: B
authors.lastname: Yameen
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA.
authors.forename: Won Il
authors.initials: WI
authors.lastname: Choi
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA; Universidad Andres Bello, Facultad de Medicina, Center for Integrative Medicine and Innovative Science (CIMIS), Echaurren 183, Santiago, Chile.
authors.forename: Cristian
authors.initials: C
authors.lastname: Vilos
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Swami
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA.
authors.forename: Jinjun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St., Boston, MA 02115, USA; King Abdulaziz University, Jeddah, Saudi Arabia. Electronic address: ofarokhzad@zeus.bwh.harvard.edu.
authors.forename: Omid C
authors.initials: OC
authors.lastname: Farokhzad
mesh_terms: D002477:Cells / Q000378:metabolism*; D004337:Drug Carriers / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D010599:Pharmacokinetics; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D004337:Drug Carriers; D004364:Pharmaceutical Preparations; D011108:Polymers
keywords: Intracellular distribution; Nanomedicine; Nanoparticle cellular uptake; Non-targeted and targeted nanoparticles; Subcellular targeting