Hydrogen Bond-Mediated Supramolecular Polymeric Nanomedicine with pH/Light-Responsive Methotrexate Release and Synergistic Chemo-/Photothermal Therapy

Abstract

Complete cancer cure and healing are still difficult, owing to its complexity and heterogeneity. Integration of supramolecular forces, for example, hydrogen bonds (H-bonds), to anti-cancer nanomedicine affords new scaffolds for biomedical material decoration, featuring the advantages of dynamic property and easier processability. Here, we target the construction of Hbond-mediated supramolecular polymer micelles, loaded with a chemotherapeutic drug along with a photothermal agent for synergistic chemo-/photothermal therapies (CT/PTT). To do so, we design and synthesize an amphiphilic ABA-type triblock copolymer, bearing H-bonding moiety (barbiturate, Ba) within the middle hydrophobic B block. The presence of pendant Ba moieties within the hydrophobic core promotes the loading capability of methotrexate (MTX) and transportation stability, benefitting from the formation of specific Ba/MTX H-bonding interactions. IR780, a photothermal agent, concomitantly encapsulated via hydrophobic interactions, facilitates the development of a synergistic CT/PTT modalities, where MTX can be released on demand owing to the dissociation of Ba/MTX H-bonding interactions induced by elevated temperature. Such H-bonding nanomedicine possesses enhanced drug loading capacity and transport performance and can also trigger stimuli-responsive drug release in the tumor zone. We believe that H-bonded nanomedicines provide a fine toolbox that is conducive to attaining biomedical requirements with remarkable values in theranostics that are highly promising in clinical applications.

Antibody-Mediated Nanodrug of Proteasome Inhibitor Carfilzomib Boosts the Treatment of Multiple Myeloma

“…Taking advantage of the “like dissolves like” mechanism, PMs-CFZ presented a decent drug loading level with a drug loading content (DLC) up to 11.2 wt % (Figure A). The introduction of extra physical interactions including π–π stacking, hydrogen bonding, and coordination has been proven to benefit drug loading and stability. − In contrast, less than 4.5 wt % of DLC was accomplished for CFZ in liposome and polycarbonate-based nanosystems. ,, DLS measurement demonstrated that PMs-CFZ had an average diameter of lower than 85 nm and a narrow distribution (PDI < 0.16).…”

Hydrogen-Bond-Driven Core-Crosslinked Supramolecular Micelles with pH/Thermal/Glutathione-Responsive Drug Release toward Enhanced Cancer Therapy

“…Importantly, certain chemotherapeutic drugs such as 5fluorouracil, methotrexate, and gemcitabine carry the configuration of specific a H-bonding array in their structure that can selectively reorganize and associate with their heterocomplementary H-bonding partners such as DAP, 32,33 barbiturate, 34 and acyclovir, 35 respectively. Chemotherapeutic drugs bearing an inherent H-bonding array reflect a particular structure merit, which can thus contribute to the principle of designing novel H-bonded supramolecular nanomedicine.…”

“…Among the diverse noncovalent interactions, the contribution of H-bonds to cancer nanomedicine − on their modality of directionality, selectivity, and sensitivity, − can function as molecular-level bonding agents for improved performance, , thus paving novel perspectives to design and create cancer nanomedicines with promising outcomes. Importantly, certain chemotherapeutic drugs such as 5-fluorouracil, methotrexate, and gemcitabine carry the configuration of specific a H-bonding array in their structure that can selectively reorganize and associate with their heterocomplementary H-bonding partners such as DAP, , barbiturate, and acyclovir, respectively. Chemotherapeutic drugs bearing an inherent H-bonding array reflect a particular structure merit, which can thus contribute to the principle of designing novel H-bonded supramolecular nanomedicine.…”

“…Drugs bonded within the nano-assemblies through H-bonding forces collectively with hydrophobic interactions exhibit promoted drug loading content and enhanced stability . In addition, stimulus-responsive and controlled drug release, sensitive to diverse parameters such as temperature, , pH, − or radiation, can be readily achieved on account of the dynamic characteristics of H-bonding interaction, improving the antitumor efficiency and reducing the toxic side effects.…”

Hydrogen-Bonded Polymer Nanomedicine with AIE Characteristic for Intelligent Cancer Therapy

“…Supramolecular nanomedicine − describes the use of H-bonds, host–guest interactions, metal chelation, and/or π–π interactions to facilitate drug solubility, prolong drug blood circulation, reduce drug premature leakage, and enhance drug loading, finally pointing to the promise to improve the pharmaceutic practice. ,, Emerging studies conducted in either in vitro or in vivo models indeed demonstrate that H-bonded nanomedicine can function as a specific therapeutic in cancer elimination, − whose properties arise from the dynamic and reversible nature of their constituents. FUA, a derivative of chemotherapeutic 5-fluorouracil (FU), is a hydrophobic antitumor agent.…”