An official website of the United States government
Fundamental synthetic methodology was advanced to allow for the preparation of a reactive glucose-based block copolycarbonate, which was conveniently transformed into a series of amphiphilic block copolymers that underwent aqueous assembly into functional nanoparticle morphologies having practical utility in biomedical and other applications. Two degradable d -glucose carbonate monomers, with one carrying alkyne functionality, were designed and synthesized to access well-defined block polycarbonates ( Đ < 1.1) via sequential organocatalytic ring opening polymerizations (ROPs). Kinetic studies of the organocatalyzed sequential ROPs showed a linear relationship between the monomer conversion and the polymer molecular weight, which indicated the controlled fashion during each polymerization. The pendant alkyne groups underwent two classic click reactions, copper-catalyzed azide–alkyne dipolar cycloaddition (CuAAC) and thiol–yne addition reactions, which were employed to render hydrophilicity for the alkyne-containing block and to provide a variety of amphiphilic diblock poly( d -glucose carbonate)s (PGCs). The resulting amphiphilic PGCs were further assembled into a family of nanostructures with different sizes, morphologies, surface charges and functionalities. These non-ionic and anionic nanoparticles showed low cytotoxicity in RAW 264.7 mouse macrophage cells and MC3T3 healthy mouse osteoblast precursor cells, while the cationic nanoparticles exhibited significantly higher IC 50 (162 μg mL −1 in RAW 264.7; 199 μg mL −1 in MC3T3) compared to the commercially available cationic lipid-based formulation, Lipofectamine (IC 50 = 31 μg mL −1 ), making these nanomaterials of interest for biomedical applications.
more »
« less
This content will become publicly available on September 16, 2026
Facile Synthesis of Diverse and Functional Nanostructures Derived from a Polyhomocysteine-Based Redox-Responsive Block Copolymer
Not AvaStimuli-responsive polypeptides offer unique advantages for biomedical applications due to their biocompatibility, degradability, and structural tunability. In this study, we report the synthesis of innovative redox-responsive polypeptide-based diblock copolymers consisting of functional disulfide-containing homocysteine derivatives and hydrophobic γ-benzyl-l-glutamate segments via sequential ring-opening polymerizations. The polymerization kinetics revealed that the polymerizations were well-controlled with living characteristics, resulting in diblock copolymers PHcy-b-PBLG with narrow molecular weight distributions. The resulting functional-hydrophobic diblock copolymers were further converted to a variety of pendant chains via thiol–disulfide exchange reactions, yielding amphiphilic polymers with tunable surface charges. These disulfide-linked materials readily self-assembled into nanoparticles in aqueous environments with hydrophobic PBLG forming the core and redox-sensitive PHcy forming the shell. The redox-responsive nanoparticles displayed a narrow size distribution, excellent colloidal stability, and excellent biocompatibility. The disulfide bonds within the polymer backbone confer redox sensitivity, allowing potential cleavage in reducing environments. Owing to their tunable surface functionality, redox-responsiveness, and biocompatibility, this platform provides a versatile route to engineer responsive nanostructures for biomedical applications, for example, positively charged nanoparticles toward nucleic acid delivery.ilable
more »
« less
- Award ID(s):
- 2238812
- PAR ID:
- 10656388
- Publisher / Repository:
- American Chemical Society
- Date Published:
- Journal Name:
- ACS Macro Letters
- Volume:
- 14
- Issue:
- 9
- ISSN:
- 2161-1653
- Page Range / eLocation ID:
- 1263 to 1268
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Ye, Qingsong (Ed.)Biodegradable and adaptable polymeric materials are currently being studied due to their wide scope of potential applications, from nanomedicine to novel multifunctional materials. One such class of polymers are poly(disulfide)s, which contain repeating disulfide bonds in their main chain. Lipoic acid, or thioctic acid, is a biologically derived small molecule containing a 1,2-dithiolane ring capable of undergoing ring opening polymerization to yield poly(disulfide)s. In this review, we highlight the synthesis of lipoic acid-based poly(disulfide)s through thermal and thiolate-initiated ring opening polymerizations, and the development of methodology pertaining to the synthetic methods. We further discuss the biomedical applications of poly(disulfide)s, which have been widely used to construct various responsive biomaterials, including polymer-drug conjugates, nanoparticles, hydrogels, and adhesives.more » « less
-
Mesoporous silica nanoparticles (MSNs) are highly porous carriers used in drug and gene delivery research for biomedical applications due to their high surface area, narrow particle size distribution, and low toxicity. Incorporating disulfide (SS) bonds into the walls of MSNs (MSN-SSs) offers a dual pathway for drug release due to the pore delivery and collapsing porous structure after cellular engulfment. This study explores the effect of embedding disulfide bonds into MSNs through various structural and biological characterization methods. Raman spectroscopy is employed to detect the SS bonds, SEM and TEM for morphology analyses, and a BET analysis to determine the required amount of SSs for achieving the largest surface area. The MSN-SSs are further loaded with doxorubicin, an anticancer drug, to assess drug release behavior under various pH conditions. The MSN-SS system demonstrated an efficient pH-responsive drug release, with over 65% of doxorubicin released under acidic conditions and over 15% released under neutral conditions. Cleaving the SS bonds using dithiothreitol increased the release to 94% in acidic conditions and 46% in neutral conditions. Biocompatibility studies were conducted using cancer cells to validate the engulfment of the nanoparticle. These results demonstrate that MSN-SS is a feasible nanocarrier for controlled-release drug delivery.more » « less
-
Abstract Instability of perovskite quantum dots (QDs) toward humidity remains one of the major obstacles for their long‐term use in optoelectronic devices. Herein, a general amphiphilic star‐like block copolymer nanoreactor strategy for in situ crafting a set of hairy perovskite QDs with precisely tunable size and exceptionally high water and colloidal stabilities is presented. The selective partition of precursors within the compartment occupied by inner hydrophilic blocks of star‐like diblock copolymers imparts in situ formation of robust hairy perovskite QDs permanently ligated by outer hydrophobic blocks via coprecipitation in nonpolar solvent. These size‐ and composition‐tunable perovskite QDs reveal impressive water and colloidal stabilities as the surface of QDs is intimately and permanently ligated by a layer of outer hydrophobic polymer hairs. More intriguingly, the readily alterable length of outer hydrophobic polymers renders the remarkable control over the stability enhancement of hairy perovskite QDs.more » « less
-
Smart, multi-stimuli-responsive nanogels that possess dynamic covalent bonds (DCBs) exhibit reversibility under equilibrium conditions allowing for controlled disassembly and release of cargo. These nanomaterials have innumerable applications in areas including drug delivery, sensors, soft actuators, smart surfaces, and environmental remediation. In this work, we implement one-pot, photo-controlled atom transfer radical polymerization-induced self-assembly (PhotoATR-PISA), mediated by UV light (λ = 365 nm) and parts per million (ppm) levels (ca. <20 ppm) of a copper(II) bromide catalyst, to fabricate dual crosslinked, polymeric nanogels with tunable orthogonal reversible covalent (TORC-NGs) core-crosslinks (CCLs). These TORC-NGs were crosslinked efficiently via coumarin photodimerization which occured simultaneously during polymerization using coumarin-functionalized methacrylate crosslinkers (CouMA). At the same time, crosslinking of nanocarriers with N,N-cystamine bismethacrylamide (CBMA) introduced orthogonal, redox-responsive, disulfide CCLs. Furthermore, incorporation of poly(glycidyl methacrylate) (PGMA) core-forming segments provided a simple handle for switchable solubility through acid-catalyzed ring-opening hydrolysis of pendant epoxide groups. In this way, the kinetics of release were tailored by the pH of the surrounding media. Thus, these TORC-NG systems showed coupled pH-, redox- and photo-responsive controlled release and disassembly behavior with full release of cargo only observed in the right sequence of stimuli and only when all three are utilized. The multi-stimuli-responsive nature of these TORC-NGs was successfully utilized herein for the controlled encapsulation and on-demand AND-gate release of hydrophobic Nile Red fluorescent reporters used as drug simulants. Various TORC-NG morphologies were synthesized in this report including nanosphere, worm-like and tubesome NGs showing variable release characteristics.more » « less
