Bioderived Lipoic Acid-Based Dynamic Covalent Nanonetworks of Poly(disulfide)s: Enhanced Encapsulation Stability and Cancer Cell-Selective Delivery of Drugs

Abstract

Dynamic covalent poly(disulfide)-based cross-linked nanoaggregates, termed nanonetworks (NNs), endowed with pH- and redox-responsive degradation features have been fabricated for stable noncovalent encapsulation and triggered cargo release in a controlled fashion. A bioderived lipoic acid-based Gemini surfactant-like amphiphilic molecule was synthesized for the preparation of nanoaggregates. It self-assembles by a entropy-driven self-assembly process in aqueous milieu. To further stabilize the self-assembled nanostructure, the core was cross-linked by ring-opening disulfide exchange polymerization (RODEP) of 1,2-dithiolane rings situated inside the core of the nanoaggregates. The cross-linked nanoaggregates, i.e., nanonetwork, are found to be stable in the presence of blood serum, and also, they maintain the self-assembled structure even below the critical aggregation concentration (CAC) as probed by dynamic light scattering (DLS) experiments. The nanonetwork showed almost 50% reduction in guest leakage compared to that of the nanoaggregates as shown by the release profile in the absence of stimuli, suggesting high encapsulation stability as evidenced by the fluorescence resonance energy transfer (FRET) experiment. The decross-linking of the nanonetwork occurs in response to redox and pH stimuli due to disulfide reduction and β-thioester hydrolysis, respectively, thus empowering disassembly-mediated controlled cargo release up to ∼87% for 55 h of incubation. The biological evaluation of the doxorubicin (DOX)-loaded nanonetwork revealed environment-specific surface charge modulation-mediated cancer cell-selective cellular uptake and cytotoxicity. The benign nature of the nanonetwork toward normal cells makes the system very promising in targeted drug delivery applications. Thus, the ease of synthesis, nanonetwork fabrication reproducibility, robust stability, triggered drug release in a controlled fashion, and cell-selective cytotoxicity behavior, we believe, will make the system a potential candidate in the development of robust materials for chemotherapeutic applications.

Thiol–Ene Click Cross-linking of Starch Oleate Films for Enhanced Properties

“…In addition, the LA-based cross-linkers have hydrophobic ends while M­(P)­A-based cross-linkers are hydrophilic end groups. This might result in the LA end groups forming a hydrophobic core around the hydrophilic PEG units, therefore shielding the effect of the hydrophilic ether groups. − This agrees with the XRD data that reveal a difference in orientation of the crystal structure for LA- and M­(P)­A- based films.…”

Tumor acidity-induced surface charge modulation in covalent nanonetworks for activated cellular uptake: targeted delivery of anticancer drugs and selective cancer cell death

“…3c and d) showed that the nanonetwork has a slightly larger size compared to the nanoassemblies due to the formation of multiple covalent bonds of β-thioesters inside the core of the nanonetwork. 68,81 The guest loaded nanonetwork was found to be even larger than that of the empty nanonetwork as probed by the DLS experiment. This could be attributed to the enlargement of the nanonetwork to make more room inside the core for the guest molecules (Fig.…”

“…However, the strategy of covalently crosslinking the core to stabilize the small molecule based nanoaggregates has shown excellent potential in the stabilization of loaded drugs and controlled release as previously reported by us and a few groups. 44,49,[66][67][68][69] To this end, we aimed to fabricate robust nanoassemblies with high stability in the vascular system and the capability of quantitative reproducibility of the building block for delivering drugs to the desired locations without leakage in the circulation pathway for successful clinical evaluation. Here we proposed the fabrication of dual pH responsive β-thioester based cross-linked nanoassemblies termed nanonetworks (NNs) from a very simple small molecular amphiphile, integrated with a tertiary amine moiety.…”

PdII Triazolylidene Complexes: Ancillary Ligand Dependent Catalytic Applications in Sonogashira Coupling and α‐Arylation Reactions under Copper‐Free Conditions

“…The DLS experiment accomplished with palladium(II) complex R-[3] and the substrates in toluene showed the presence of nanoaggregates with an average diameter of 190.62 nm, whereas the DSL data with the reaction mixture containing active pre-catalyst R-[4] showed an average particle diameter of 0.83 nm. [22] It is believed that the inactive nature of the complex R-[3] in the αarylation of 1-methyl-2-oxindole is due to the alteration of the molecular complex to palladium nanoparticles (PdÀ NPs). A black color precipitate was observed when the reaction mixture was heated in the presence of complex R-[3], which is possibly due to the PdÀ NPs (see Supporting Information).…”

“…The dynamic light scattering (DLS) measurement has also been conducted to indicate the formation of the Pd−NPs in the reaction mixture containing R ‐[ 3 ] (Figure 3). The DLS experiment accomplished with palladium(II) complex R ‐[ 3 ] and the substrates in toluene showed the presence of nanoaggregates with an average diameter of 190.62 nm, whereas the DSL data with the reaction mixture containing active pre‐catalyst R ‐[ 4 ] showed an average particle diameter of 0.83 nm [22] . It is believed that the inactive nature of the complex R ‐[ 3 ] in the α ‐arylation of 1‐methyl‐2‐oxindole is due to the alteration of the molecular complex to palladium nanoparticles (Pd−NPs).…”