Nanocrystals Slow-Releasing Ropivacaine and Doxorubicin to Synergistically Suppress Tumor Recurrence and Relieve Postoperative Pain

Abstract

Although surgical resection provides a straightforward and effective treatment for most malignant solid tumors, tumor recurrence and acute postoperative pain continue to be two big problems associated with this treatment. To resolve these problems, a nanocrystal composite slow-releasing ropivacaine and doxorubicin was fabricated in this study. Briefly, a self-assembling peptide was used to form nanoparticle complexes with the two drugs, based on which homogeneous nanocrystals were obtained by adjusting the pH. In cultured human melanoma cells, the nanocrystals exhibited improved antitumor activity due to a synergistic effect and enhanced cellular uptake of the two drugs. On the other hand, the nanocrystals could slowly release ropivacaine in vitro and in vivo, generating long-acting analgesia on the rat sciatic nerve block model and incisional pain model. On a nude mouse tumor resection model, the nanocrystals simultaneously suppressed the recurrence of solid tumor and relieved postoperative pain, indicating a potential postoperative treatment for tumor resection patients. This nanocrystal system also suggested a promising and facile strategy for developing multifunctional formulations combining different drugs, which could achieve better therapeutic outcomes in a synergistic and sustained manner.

Size control of ropivacaine nano/micro-particles by soft-coating with peptide nanosheets for long-acting analgesia

“…At pre-set time intervals, a proper volume of dialysis buffer was extracted and fresh PBS of the equal volume was added into the centrifuge tube. The concentration of released ropivacaine at different time point was measured by HPLC as previously described 23 , and the cumulative drug release rate was calculated accordingly.…”

“…As a novel type of carrier materials for advanced drug delivery systems, self-assembling peptides (SAPs) composed of natural amino acids have attracted more and more attention for their excellent biocompatibility and biodegradability 18 - 20 . In our previous studies, SAPs were used to form nanoparticle complexes with soluble LA hydrochlorides, which could induce the bottom-up formation of slow-releasing LA nano/micro-crystals with prolonged analgesic duration and considerable safety 21 - 23 .…”

Two-Dimensional Molecular Architectonics through Controlled Noncovalent Interactions: Structure, Functional Properties, and Applications

“…Achieving precise control over noncovalent interactions at the molecular level is a challenging task in mastering the art of engineering molecular organization into functional architectures. In this context, the strategy of engineering molecular assemblies of designer modular functional cores by functionalizing with suitable biomolecules or their biomimetics as auxiliaries to fabricate functional 1D, 2D, 3D, and hierarchical architectures of well-defined shape, size, and properties is conceptualized as molecular architectonics. − In recent years, 2D architectures have gained prominence due to their exotic structure, properties, and applications. − The scheme of molecular architectonics allows the fabrication of molecular and material architectures through 2D molecular organization, offering vast opportunities. − ,− In nature, biomolecules have built-in information for molecular recognition to undergo ordered and hierarchical molecular organization through controlled and synchronized noncovalent interactions to form biological materials of varied dimension and hierarchy with predefined structure and functions. The development of 2D material architectures by adopting nature-inspired design strategies addresses problems in the domains of health, energy, and environment. − Molecular architectonics guide the fabrication of 2D material architectures with functional properties and technological applications .…”