Host−Guest Interaction Mediated Polymeric Assemblies: Multifunctional Nanoparticles for Drug and Gene Delivery

Abstract

Novel core-shell structured nano-assemblies are assembled by a β-cyclodextrin containing positively charged host polymer and a hydrophobic guest polymer. The hydrophobic core of this type of assemblies serves as a nano-container to load and release the hydrophobic drugs, while the positively charged hydrophilic shell is able to condense the plasmid DNA and achieve its transfection/ expression in osteoblast cells. These assemblies may be used as a new generation of multi-functional nano-carriers for simultaneous drug delivery and gene therapy. Keywordshost-guest interactions; polymer assemblies; multifunctional nanoparticles; drug delivery; gene delivery Multi-functionalized nanocarriers are attractive in pharmaceutics, medical imaging, biomedical engineering, and gene therapy. 1 For instance, drug delivery, cell targeting and/or multi-modal imaging can be simultaneously achieved by multifunctional inorganic nanoparticles or nanocrystals, inorganic-organic hybrid nanoparticles and polymeric assemblies. [2][3][4][5][6][7][8][9] Studies based on these versatile pharmaceutical nanocarriers have provided profound insights on the intracellular or in vivo distribution, and valuable information on the spatial and temporal interactions of delivery carriers with cells and tissues as well as their intracellular interactions. In addition, multi-functional nanoparticles have also been employed to implement the simultaneous gene delivery, drug delivery and imaging. 6,[10][11][12][13][14] Using cyanine dye (Cy5.5) labeled magnetic nanoparticles conjugated to a synthetic small interfering RNA (siRNA) duplex, Moore and coworkers were able to achieve the in vivo transfer of siRNA and the simultaneous imaging of its accumulation in tumors by high-resolution magnetic resonance imaging and near-infrared in vivo optical imaging. 15 Proton-sponge coated quantum dots were employed by Nie and Gao et al. for siRNA delivery and intracellular imaging. 16 While these nanocarriers allow the real-time tracking and ultrastructural localization of siRNA delivery system, combining drug delivery and gene therapy in one particle has the potential to *To whom correspondence should be addressed: Prof. Peter X Ma, Department of Biologic and Materials Sciences, Macromolecular Science and Engineering Center, Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; mapx@umich.edu. Supporting Information Available. 1 H NMR, FT-IR and fluorescence spectra, and titration curves. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public AccessAuthor Manuscript ACS Nano. Author manuscript; available in PMC 2011 February 23. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript enhance the transfection efficiency or to achieve a synergistic/combined effect of drug and gene therapies. [17][18][19][20] By co-delivering inflammatory suppressors and plasmid DNA (pDNA) through liposomes, Huang and coworkers developed a non-immunostimulatory gene vector (safeplex), which...

Gene therapy for C-26 colon cancer using heparin-polyethyleneimine nanoparticle-mediated survivin T34A

“…33 Cationic nanoparticles can be used as a nonviral gene vector in vitro and in vivo. [34][35][36] PEI is one of the most efficient nonviral gene transfection agents. However, PEI is not biodegradable and has high cytotoxicity, which greatly restricts its clinical application.…”

Application of Nanoparticles in Manufacturing

“…A major application is in the biomedical area as a carrier for drug/gene delivery [300,327,343,485], biomarkers [205], and agrochemicals in plants [383], as nanoparticles can often cross physiological barriers and reach different tissues in a controllable style. Various particles have been reported, including polymeric [101], silica [365,410], magnetic [236,295,404], noble metal (especially Au nanoparticles) [12,90], quantum dots [347], lipid [7,29,230], micelles [189], dendrimers [313], hybrid structures [143,144], and even the new emerging nano-diamond [268].…”

Multifunctional Polymeric Nano-Carriers in Targeted Drug Delivery

“…In line with the author's hypothesis, the developed nano-assemblies exhibited excellent transfection and lower cytotoxicity in MC3T3-E1 osteoblast cells. Furthermore, presence of functionally active amine groups at the periphery supposed to provide additional functionalities to proposed system [ 145 ]. Cyclodextrin based systems, ornamented with different varieties of ligands, have also been reported for targeted gene delivery.…”