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Carbon Nanotubes Used as Nanocarriers in Drug and Biomolecule Delivery
Published in Raj K. Keservani, Anil K. Sharma, Rajesh K. Kesharwani, Drug Delivery Approaches and Nanosystems, 2017
Hua He, Deli Xiao, Lien Ai Pham-Huy, Pierre Dramou, Chuong Pham-Huy
Unlike various small molecules (drugs, hormones, etc.) which are able to diffuse into cells, macrobiomolecules (proteins, DNA, and RNA) rarely cross cell membranes by themselves. Intracellular delivery is thus required in order to use these molecules for therapeutic applications. For example, proteins can be either covalently conjugated or noncovalently adsorbed on CNTs for intracellular delivery (Li et al., 2008; Pantarotto et al., 2004). The hydrophobic surface of partially oxidized SWCNTs allows nonspecific binding of proteins. After being translocated into cells by nanotubes, proteins can become bioactive once they are released from endosomes (Li et al., 2008; Pantarotto et al., 2004). The use of functionalized CNTs as nanocarriers in macrobiomolecule delivery is a promising tool for the treatment of different dreadful ailments such as cancer in the future.
Engineering Nanoparticles to Overcome Barriers to Immunotherapy
Published in Raj Bawa, János Szebeni, Thomas J. Webster, Gerald F. Audette, Immune Aspects of Biopharmaceuticals and Nanomedicines, 2019
With all of these intracellular delivery strategies, it is important to consider the balance between efficient delivery and toxicity and immunogenicity. Cationic polymers, while effective at facilitating endosomal escape, also may induce cytotoxicity at high doses. Traditional cell penetrating peptides, which permeate the cell membrane, also will cause harm to cells at very high doses [126]. If new fusogenic viral peptides are conjugated to a nanoparticle, it is essential to evaluate if their systemic immunogenicity are outweighed by the increased therapeutic efficacy which is enabled by more site-specific intracellular delivery.
Effect of lipopolysaccharide addition on the gene transfection of spermine-introduced pullulan-plasmid DNA complexes for human mesenchymal stem cells
Published in Journal of Biomaterials Science, Polymer Edition, 2019
Masumi Ueda, Jun-Ichiro Jo, Jian-Qing Gao, Yasuhiko Tabata
Comprehensively considering the results obtained, it is possible that the balance of cytotoxicity, cellular internalization of complexes, and cell cycle after LPS treatment results in the enhanced gene transfection at a certain LPS concentration. The present procedure of LPS cell stimulation is a promising and new technology to enhance the level of gene transfection. This can be applied to other types of cells. On the other hand, it should be noted that the immortalized hMSC were used in this study and certain primary cells have a strong innate immune response to LPS. In this study, spermine-pullulan was used as a carrier for the intracellular delivery of plasmid DNA. The optimal concentration of LPS may be changed by altering the carriers for gene transfection such as Lipofectamine® 2000 etc. Further examination is still needed to make clear the mechanism on the efficiency of non-viral gene transfection.
FA and cRGD dual modified lipid-polymer nanoparticles encapsulating polyaniline and cisplatin for highly effective chemo-photothermal combination therapy
Published in Journal of Biomaterials Science, Polymer Edition, 2018
Zhiguo Gao, Chaoqun You, Hongshuai Wu, Mingxin Wang, Xiangyang Zhang, Baiwang Sun
Subsequently, the intracellular delivery efficiency of nanoparticles into MDA-MB-231 cells was implemented using confocal laser scanning microscopy (CLSM) in our study. We selected targeted FA/cRGD-PNPs and non-targeted PNPs as research objects, and took picture at certain time interval after being incubated with them. As showed in Figure 6(A), with the extension of incubation time, the strong green fluorescence gradually spread to the cytoplasm and even the nucleus of cells, which demonstrated that the released cisplatin from cracked nanoparticles had spread from cytoplasm to the cell nucleus. As shown in Figure 6(B), MDA-MB-231 cells incubated with targeted FA/cRGD-PNPs showed strikingly stronger green fluorescence intensities than non-targeted PNPs at the same time interval. The intracellular delivery performance of nanoparticles into MDA-MB-231 cells indicated that cRGD cyclic peptide and folate acid ligand specifically bound receptors overexpressed on the surface of the cell membrane. These results indicated that prepared nanoparticles possessed a good biological compatibility and could be easily endocytosed by cells, further achieving high targeting efficiency due to the targeting role of cRGD cyclic peptide and folate acid ligand.
Disulfide proteinoid micelles responsive to reduction
Published in Journal of Dispersion Science and Technology, 2019
Kyeongnan Kwon, Danbi Park, Jin-Chul Kim
The localization of a therapeutic agent into target cells is necessary to increase the efficacy without the acute toxicity. One of the strategies to deliver a therapeutic agent intracellularly is to take advantage of reduction-responsive carriers.[1–7] Since the intracellular space is reductive due to the relatively high concentration of glutathione (a reducing agent), reduction-responsive carriers are able to release their content mainly within cells as long as they can be taken up by cells.[8,9] As a building block of reduction-responsive carriers, disulfide compounds have been frequently used because they can be reduced to thiol compounds in reducing condition.[10–12] Upon the reduction, the integrity of drug carriers can be deteriorated. For example, drug carriers are broken down, and the wall and/or the matrix are loosened. As a result, the drug carriers composed of disulfide compounds could actively release their content when their environment is reductive. Poly(ethyleneimine) (PEI) cross-linked by disulfide bond was used for the intracellular delivery of DNA and it was reported to enhance the transfection efficiency.[13–15] Poly(ε-caprolactone) and poly(ethyl ethylene phosphate) were linked by disulfide bond and the copolymer was used to prepare a reduction-responsive nanoparticle for the intracellular delivery of doxorubicin.[16,17] A copolymer composed of a monomer attaching alkyl chain through disulfide bond and a hydrophilic monomer was self-assembled into micelle in aqueous phase. The micelle was disassembled due to the cleavage of the disulfide bond when it was exposed to reducing condition.[18,19] Poly(ethylene glycol) and poly(propylene sulfide) were linked by disulfide bond and the block copolymer was used for the preparation of polymersome.[1] The disulfide bond of the copolymer chain was broken down in reducing condition and the polymeric vesicles were disintegrated. Besides the reduction-responsive drug carriers described above, there have been developed hyper-branched polymers, nanogels, and layer-by-layer capsules as reduction-responsive carriers by utilizing the reducible property of disulfide bond.[20–23] Recently, dithiopropionic acid-crosslinked PEI gel was included in the water channel of MO cubic phase to make it release its payload in a reduction-responsive manner.[24]