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Reduction sensitive micelles with variable cell penetrating ability for triggered intracellular drug release
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ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575
targeting nanoparticle efficiently promoted the transfection and migration of endothelial cells. Therefore, they have the potential as safe and efficient gene carriers, and might enhance the rapid endothelialization of artificial blood vessels.
Functional surfactants: designing principles and applications in constructing nanomedicines Xiang Gao, Peng Zhang, Xiaolan Zhang, Yixian Huang, Jianqing Lu, Song Li University of Pittsburgh, School of Pharmacy, Hisun Pharmaceutical (Hang Zhou). Co. Ltd., Zhejiang Province, China
http://dx.doi.org/10.1016/j.nano.2015.12.031
The structure of building blocks or components often has a significant impact on the performance of nanoparticles as drug carriers. It is well known that many micelle, emulsion, and liposome formulations have low drug loading efficiency and inadequate formulation stability issues toward many drugs that are neither very hydrophobic, nor very hydrophilic. We hypothesize that much of that can be attributed to poor compatibility between drug and carrier molecules, and by introducing “drug-friendly” chemical groups that potentially interact with drug to carrier molecule, one should ease the compatibility issue. We tested this by designing several new surfactants equipped with various aromatic structural elements, placed at interface region, and used these to form nanostructures together with a panel of model drugs. The results clearly showed that the addition of aromatic structures indeed had a significant effect on improving drug loading and formulation stability for lipid-based micelles and emulsion formulations. The drugs thus formulated had a significantly improved in vivo performance both in terms tissue distribution and therapeutic effects in several animal models. Our approach provides new insides in structure-activity relationship in surfactant-based drug carriers and may have practical application in the development of improved drug nanoformulations. Supported by NIH funds R21CA172887, RO1CA174305, and RO1GM102989.
Reduction sensitive micelles with variable cell penetrating ability for triggered intracellular drug release Tong Shen, Qingsong Yu⁎, Zhihua Gan⁎, The State Key Laboratory of Organic-inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, China ⁎Corresponding authors. E-mail addresses: [email protected] (Q. Yu), [email protected] (Z. Gan) In this work, poly(ethylene oxide)-b-poly(N-methacryloyl-N′-(tert-butyloxy carbonyl) cystamine) (PEO-b-PMABC) diblock copolymers were developed by reversible addition-fragmentation chain transfer (RAFT) polymerization according to our previous work1 for triggered intracellular drug release. In order to control the cell penetrating ability, as-prepared micelles were treated by different amount of trifluoric acid (TFA). The deprotection process was monitored by 1H NMR, DLS and zetasizer, respectively. The cellular uptake of polymeric micelles by Hela cells was characterized by confocal laser scanning microscopy (CLSM) and flow cytometry. As shown in Figure 1, c and d, with the gradual removal of protection groups via addition of acid, the micelles showed the slowly increase of size, and finally collapsed when the volume of acid reached a critical value. It is interesting that the zeta potential of TFA treated micelles did not undergo rapid change after treatment. Relatively slow conversion of the zeta potential from negative value to positive value was observed. In contrast to this, micelles formed by polymer treated with TFA/DMSO, which was thought to be randomly deprotected, showed no time dependent zeta potential conversion. This indicated that the deprotection process of polymeric micelle is in a gradual way from outer shell to inner core. The cellular uptake of polymeric micelles treated by different amount of TFA was shown in Figure 1, e. It can be found that micelles with different deprotection degree showed significant difference in cell uptake level, which indicated their different penetrating ability into cells. This result proved that the amount of positive charge on the hydrophilic shell of TFA treated micelles is different from each other. The quantitative analysis of the cellular uptake (data not show here) showed that the disulphide bond plays an important role in drug release inside cells. Above all, this work presented an experimental simulation of the typical acidresponse process of the acid labile polymeric micelles. In the meantime, this work reported a facile route to obtain reduction-sensitive micelles with variable cell penetrating ability.
Figure 1. (a) Schematic illustration of the formation of micelle and the reduction-triggered disassembly of PEO-b-PMABC micelles and intracellular drug release. (b) Schematic illustration of the deprotection procedure. (c) The size alteration after TFA treatment. (d) Time dependence of zeta potential for TFA treated micelles. (e) CLSM images of Hela cells incubated with Dox-loaded micelles treated by TFA for different time and free Dox.
http://dx.doi.org/10.1016/j.nano.2015.12.032
http://dx.doi.org/10.1016/j.nano.2015.12.033
Design and fabrication of upconversion nanoparticles for biomedical applications Zhanjun Gu, Gan Tian, Yuan Yong, Yuliang Zhao, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China E-mail address: [email protected] (Z. Gu) Lanthanide (Ln) doped upconversion nanoparticles (UCNPs) have attracted enormous attention in the recent years due to their unique upconversion luminescent properties that enable the conversion of low-energy photons (near infrared photons) into highenergy photons (visible to ultraviolet photons) via the multiphoton processes. This feature makes them ideal for bioimaging applications with attractive advantages such as no autofluorescence from biotissues and a large penetration depth. In addition, by incorporating advanced features, such as specific targeting, multimodality imaging and therapeutic delivery, the application of UCNPs has been dramatically expanded. In this presentation, we first summarize the recent developments in the fabrication strategies of UCNPs with the desired size, enhanced and tunable upconversion luminescence, as well as the combined multifunctionality. We then discuss the chemical methods applied for UCNPs surface functionalization to make these UCNPs biocompatible and water-soluble, and further highlight some representative examples of using UCNPs for in vivo bioimaging, NIR triggered drug delivery applications and photodynamic therapy. The UCNPs can actually provide an ideal multifunctionalized platform for solutions to many key issues in the front of medical sciences such as theranostics, individualized therapeutics, multimodality medicine, etc.
Figure 1. Design of upconversion nanoparticles for bioimaging and therapy.
http://dx.doi.org/10.1016/j.nano.2015.12.034
ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575
targeting nanoparticle efficiently promoted the transfection and migration of endothelial cells. Therefore, they have the potential as safe and efficient gene carriers, and might enhance the rapid endothelialization of artificial blood vessels.
Functional surfactants: designing principles and applications in constructing nanomedicines Xiang Gao, Peng Zhang, Xiaolan Zhang, Yixian Huang, Jianqing Lu, Song Li University of Pittsburgh, School of Pharmacy, Hisun Pharmaceutical (Hang Zhou). Co. Ltd., Zhejiang Province, China
http://dx.doi.org/10.1016/j.nano.2015.12.031
The structure of building blocks or components often has a significant impact on the performance of nanoparticles as drug carriers. It is well known that many micelle, emulsion, and liposome formulations have low drug loading efficiency and inadequate formulation stability issues toward many drugs that are neither very hydrophobic, nor very hydrophilic. We hypothesize that much of that can be attributed to poor compatibility between drug and carrier molecules, and by introducing “drug-friendly” chemical groups that potentially interact with drug to carrier molecule, one should ease the compatibility issue. We tested this by designing several new surfactants equipped with various aromatic structural elements, placed at interface region, and used these to form nanostructures together with a panel of model drugs. The results clearly showed that the addition of aromatic structures indeed had a significant effect on improving drug loading and formulation stability for lipid-based micelles and emulsion formulations. The drugs thus formulated had a significantly improved in vivo performance both in terms tissue distribution and therapeutic effects in several animal models. Our approach provides new insides in structure-activity relationship in surfactant-based drug carriers and may have practical application in the development of improved drug nanoformulations. Supported by NIH funds R21CA172887, RO1CA174305, and RO1GM102989.
Reduction sensitive micelles with variable cell penetrating ability for triggered intracellular drug release Tong Shen, Qingsong Yu⁎, Zhihua Gan⁎, The State Key Laboratory of Organic-inorganic Composites, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, China ⁎Corresponding authors. E-mail addresses: [email protected] (Q. Yu), [email protected] (Z. Gan) In this work, poly(ethylene oxide)-b-poly(N-methacryloyl-N′-(tert-butyloxy carbonyl) cystamine) (PEO-b-PMABC) diblock copolymers were developed by reversible addition-fragmentation chain transfer (RAFT) polymerization according to our previous work1 for triggered intracellular drug release. In order to control the cell penetrating ability, as-prepared micelles were treated by different amount of trifluoric acid (TFA). The deprotection process was monitored by 1H NMR, DLS and zetasizer, respectively. The cellular uptake of polymeric micelles by Hela cells was characterized by confocal laser scanning microscopy (CLSM) and flow cytometry. As shown in Figure 1, c and d, with the gradual removal of protection groups via addition of acid, the micelles showed the slowly increase of size, and finally collapsed when the volume of acid reached a critical value. It is interesting that the zeta potential of TFA treated micelles did not undergo rapid change after treatment. Relatively slow conversion of the zeta potential from negative value to positive value was observed. In contrast to this, micelles formed by polymer treated with TFA/DMSO, which was thought to be randomly deprotected, showed no time dependent zeta potential conversion. This indicated that the deprotection process of polymeric micelle is in a gradual way from outer shell to inner core. The cellular uptake of polymeric micelles treated by different amount of TFA was shown in Figure 1, e. It can be found that micelles with different deprotection degree showed significant difference in cell uptake level, which indicated their different penetrating ability into cells. This result proved that the amount of positive charge on the hydrophilic shell of TFA treated micelles is different from each other. The quantitative analysis of the cellular uptake (data not show here) showed that the disulphide bond plays an important role in drug release inside cells. Above all, this work presented an experimental simulation of the typical acidresponse process of the acid labile polymeric micelles. In the meantime, this work reported a facile route to obtain reduction-sensitive micelles with variable cell penetrating ability.
Figure 1. (a) Schematic illustration of the formation of micelle and the reduction-triggered disassembly of PEO-b-PMABC micelles and intracellular drug release. (b) Schematic illustration of the deprotection procedure. (c) The size alteration after TFA treatment. (d) Time dependence of zeta potential for TFA treated micelles. (e) CLSM images of Hela cells incubated with Dox-loaded micelles treated by TFA for different time and free Dox.
http://dx.doi.org/10.1016/j.nano.2015.12.032
http://dx.doi.org/10.1016/j.nano.2015.12.033
Design and fabrication of upconversion nanoparticles for biomedical applications Zhanjun Gu, Gan Tian, Yuan Yong, Yuliang Zhao, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China E-mail address: [email protected] (Z. Gu) Lanthanide (Ln) doped upconversion nanoparticles (UCNPs) have attracted enormous attention in the recent years due to their unique upconversion luminescent properties that enable the conversion of low-energy photons (near infrared photons) into highenergy photons (visible to ultraviolet photons) via the multiphoton processes. This feature makes them ideal for bioimaging applications with attractive advantages such as no autofluorescence from biotissues and a large penetration depth. In addition, by incorporating advanced features, such as specific targeting, multimodality imaging and therapeutic delivery, the application of UCNPs has been dramatically expanded. In this presentation, we first summarize the recent developments in the fabrication strategies of UCNPs with the desired size, enhanced and tunable upconversion luminescence, as well as the combined multifunctionality. We then discuss the chemical methods applied for UCNPs surface functionalization to make these UCNPs biocompatible and water-soluble, and further highlight some representative examples of using UCNPs for in vivo bioimaging, NIR triggered drug delivery applications and photodynamic therapy. The UCNPs can actually provide an ideal multifunctionalized platform for solutions to many key issues in the front of medical sciences such as theranostics, individualized therapeutics, multimodality medicine, etc.
Figure 1. Design of upconversion nanoparticles for bioimaging and therapy.
http://dx.doi.org/10.1016/j.nano.2015.12.034