[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

https://cyberleninka.org/article/n/933162.pdf

Hydrogels in drug delivery: progress and challenges

Molecular self-assembly is the spontaneous association of molecules under equilibrium conditions into stable, structurally well-defined aggregates joined by noncovalent bonds. Molecular self-assembly is ubiquitous in biological systems and underlies the formation of a wide variety of complex biological structures. Understanding self-assembly and the associated noncovalent interactions that connect complementary interacting molecular surfaces in biological aggregates is a central concern in structural biochemistry. Self-assembly is also emerging as a new strategy in chemical synthesis, with the potential of generating nonbiological structures with dimensions of 1 to 10(2) nanometers (with molecular weights of 10(4) to 10(10) daltons). Structures in the upper part of this range of sizes are presently inaccessible through chemical synthesis, and the ability to prepare them would open a route to structures comparable in size (and perhaps complementary in function) to those that can be prepared by microlithography and other techniques of microfabrication.

Molecular self-assembly and nanochemistry: A chemical strategy for the synthesis of nanostructures

https://www.farm.ucl.ac.be/Full-texts-FARM/Danhier-2010-2.pdf

To exploit the tumor microenvironment: Passive and active tumor targeting of nanocarriers for anti-cancer drug delivery

/pdf/degradable-controlled-release-polymers-and-polymeric-1y322ha58z.pdf

Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release

To overcome cancer-associated immunosuppression, we prepared a dual-targeting vector to deliver CpG oligodeoxynucleotides (ODN) to macrophages. The dual-targeting system composed of mannosylated carboxymethyl chitosan (MCMC)/hyaluronan (HA) for macrophage targeting and protamine sulfate for ODN complexation was prepared by self-assembly. The effects of ODN delivery on immune cells was studied in J774A.1 cells. Due to the enhanced delivery efficiency, the dual-targeting delivery system exhibits a higher immune stimulatory activity compared with the monotargeting delivery system containing either MCMC or HA, resulting in a dramatically enhanced secretion of proinflammatory cytokines and a successful shift to activated macrophages (M1). Besides macrophages, the influence of the delivery system on tumor cells (MCF-7) was also investigated. In MCF-7 cells, the increased expressions of nuclear transcription factor-κB (NF-κB), PIK3R3, and phosphorylated protein kinase B (p-Akt) caused by activated NF-κB and phosphoinositide 3-kinase/Akt signalings were observed. Nevertheless, upregulated Fas as well as Fas ligand (FasL) may induce Fas/FasL-mediated apoptosis, which results in the increased expressions of caspases in tumor cells.

A Dual Macrophage Targeting Nanovector for Delivery of Oligodeoxynucleotides To Overcome Cancer-Associated Immunosuppression.

An amphiphilic, biotinylated poly(N-isopropylacrylamide-co-N-(3-dimethylamino propyl)methacrylamide)-block- poly(?-caprolactone) (biotin-P(NIPAAm-co-NDAPM)- b-PCL) block copolymer was synthesized. The cytotoxicity study showed that the copolymer exhibited no apparent cytotoxicity. In aqueous solution, biotin-P(NIPAAm-co-NDAPM)- b-PCL copolymer was able to self-assemble into micelles of around 60?nm in diameter with a critical micellar concentration (CMC) of 36?mg?l?1. Biotin-P(NIPAAm- co-NDAPM)-b-PCL micelles were thermo-responsive and the cloud point temperature was at 36.5??C. The fluorescent group, fluorescein isothiocyanate (FITC) was further introduced to label the biotin-P(NIPAAm-co-NDAPM)- b-PCL copolymer. A cell internalization experiment was conducted and it was found that the fluorescent micelles could be internalized into the cells. The drug release behavior of drug-loading micelles was also examined and the drug-loaded biotin-P(NIPAAm-co-NDAPM)- b-PCL micelles showed slow drug release at 27??C and fast drug release at 37??C.

https://iopscience.iop.org/article/10.1088/0957-4484/18/50/505101/pdf

Fluorescent, thermo-responsive biotin-P(NIPAAm-co-NDAPM)-b-PCL micelles for cell-tracking and drug delivery

Novel cholic acid functionalized star oligo/poly(DL-lactide)s with different molecular weights were synthesized through the ring-opening polymerization of DL-lactide initiated by cholic acid. Compared with poly(DL-lactide), these star oligo/poly(DL-lactide)s show faster hydrolytic degradation rates, and the degradation mechanism changes from bulk erosion to surface erosion with decreasing molecular weight. Based on the specific physicochemical properties of the novel star oligo/poly(DL-lactide), the drug delivery system with submicron size was fabricated using a very convenient "ultrasonic dispersion method" which did not involve toxic organic solvents. The in vitro drug release was studied.

Novel cholic acid functionalized star oligo/poly(DL-lactide)s for biomedical applications.

To achieve effective tumor eradication using anti-tumor immunotherapies, a fusion peptide functionalized gene delivery system for macrophage and tumor targeting delivery of the plasmid DNA encoding the IL-12 gene (pDNA IL-12) was prepared for macrophage re-polarization as well as reversal of cancer immunosuppression. A fusion peptide containing the tuftsin sequence that can interact with Fc receptors and neuropilin-1, and hyaluronic acid (HA) that can interact with CD44 were introduced into the delivery system by self-assembly to form peptide/hyaluronic acid/protamine/CaCO3/DNA nanoparticles (PHNP) with both macrophage targeting and tumor targeting capabilities. PHNP provides an efficient immunoregulation on J774A.1 cells to shift the anti-inflammatory M2 phenotype to the anti-tumor M1 phenotype with enhanced secretion of pro-inflammatory cytokines and increased expression of M1 markers. Owing to the improved delivery efficiency caused by the fusion peptide and HA, the transfection mediated by multi-functional PHNP can up-regulate IL-12 as well as down-regulate IL-10 and IL-4 more effectively as compared with the nanoparticles without HA and/or peptide decoration. More importantly, the gene delivery system can also deliver pDNA IL-12 to targeted cancerous HeLa cells to realize the secretion of IL-12. PHNP not only enables tumorous cells to produce pDNA IL-12, but also down-regulates CD47 and up-regulate CD80 and HLA-1 in the malignant cells, indicating that the gene delivery system can effectively reverse tumor induced immunosuppression.

A multi-functional macrophage and tumor targeting gene delivery system for the regulation of macrophage polarity and reversal of cancer immunoresistance.

A series of amphiphilic pH-sensitive hybrid polypeptide copolymers, poly(ethylene glycol)-b-poly(L-lysine)-b-poly(L-phenylalanine) (PEG-PLL-PLP) were synthesized. The copolymers could self-assemble into micelles with PLP as the hydrophobic core and PEG-PLL as the hydrophilic shell, as evidenced by 1HNMR and TEM. These micelles exhibited obvious pH response in hydrodynamic diameter and pH-dependent drug release behavior, attributed to the protonation/deprotonation of amino groups in PLL segments. The copolymers could further condense plasmid DNA efficiently. Importantly, the polymer/DNA complexes showed high transfection efficiency in 293T cells under optimized conditions. This study suggested the copolymers may have great potential in both drug and gene delivery.

Si-Xue Cheng

Papers

A Dual Macrophage Targeting Nanovector for Delivery of Oligodeoxynucleotides To Overcome Cancer-Associated Immunosuppression.

Fluorescent, thermo-responsive biotin-P(NIPAAm-co-NDAPM)-b-PCL micelles for cell-tracking and drug delivery

Novel cholic acid functionalized star oligo/poly(DL-lactide)s for biomedical applications.

A multi-functional macrophage and tumor targeting gene delivery system for the regulation of macrophage polarity and reversal of cancer immunoresistance.

Dual-vectors of anti-cancer drugs and genes based on pH-sensitive micelles self-assembled from hybrid polypeptide copolymers