Natural Chlorogenic Acid Planted Nanohybrids with Steerable Hyperthermia for Osteosarcoma Suppression and Bone Regeneration

Abstract

Surgical resection is the most common approach for the treatment of osteosarcoma. However, two major complications, including residual tumor cells and large bone defects, often arise from the surgical resection of osteosarcoma. Discovering new strategies for programmatically solving the two above‐mentioned puzzles has become a worldwide challenge. Herein, a novel one‐step strategy is reported for natural phenolic acid planted nanohybrids with desired physicochemical properties and steerable photothermal effects for efficacious osteosarcoma suppression and bone healing. Nanohybrids are prepared based on the self‐assembly of chlorogenic acid and gold nanorods through robust Au‐catechol interface actions, featuring precise nanostructures, great water solubility, good stability, and adjustable hyperthermia generating capacity. As expected, on the one hand, these integrated nanohybrids can severely trigger apoptosis and suppress tumor growth with strong hyperthermia. On the other hand, with controllable mild NIR irradiation, the nanohybrids promote the expression of heat shock proteins and induce prominent osteogenic differentiation. This work initiates a brand‐new strategy for assisting osteosarcoma surgical excision to resolve the blockage of residual tumor cells elimination and bone regeneration.

Osteogenic mechanism of chlorogenic acid and its application in clinical practice

“…These nanohybrids triggered apoptosis and inhibited the growth of osteosarcoma. Additionally, under controlled mild near-infrared irradiation, the nanohybrids stimulated cellular osteogenic differentiation by upregulating Hsp47 and Hsp70 genes and promoting the expression of heat shock proteins ( Yang et al, 2023 ).…”

Bone-Targeted Supramolecular Nanoagonist Assembled by Accurate Ratiometric Herbal-Derived Therapeutics for Osteoporosis Reversal

“…51,52 On the other hand, chlorogenic acid (CGA), a type of phenolic acid from Lonicera japonica, also exhibits antioxidation, anti-inflammatory, and bone formation properties. 32,53 Recently, more and more researches indicate that both BER and CGA act as potential small-molecule agonists of the Wnt signaling pathway. 54,55 Herein, we develop accurate ratiometric nanoagonists (NAs) derived from herbal medicine with the desired potential of accelerating bone formation via inducing Wnt signaling for conquering osteoporosis (Scheme 1).…”

“…There is an increasing acknowledgment of TCM as a promising reservoir of clinical agents based on the proven effectiveness of numerous bioactive ingredients. , The Wnt signaling pathway plays an important role in regulating bone metabolism, opening novel innovations in osteoporosis treatment. − With the development of biomedical technologies, many kinds of bioactive ingredients have been identified as potential agonists of Wnt signaling pathway with good osteogenic abilities, which opens a brand-new way for osteoporosis therapy. , Combinational administration of multiple bioactive ingredients plays a particularly prominent role in the treatment of bone diseases, which follows the conventional wisdom that “more is better” like TCMs. , However, because of their small molecular size, nearly all of constituents sustain several restrictions, such as high dose requirement, poor bioavailability, and rapid blood clearance. − To settle the above limitations, some nanoplatforms have been used as drug co-carrier systems to overcome the drawbacks and improve therapeutic efficacy. − Unfortunately, carrier-assisted codelivery systems suffer from complex preparation, poor drug loading ability, apparent carrier-induced toxicity, and severe immunogenicity within the human body . Moreover, current tactics that rely on nanoplatforms for combination therapy often encounter challenges related to unclear dose ratios and uncontrolled active ingredients.…”

“…According to drug combination in TCM, Coptidis rhizome and Lonicera japonica are a pair of herbs to clear away heat and toxins. On the one hand, berberine (BER), a kind of alkaloid from Coptidis rhizome , displays antibacterial, antiviral, and osteogenic properties. , On the other hand, chlorogenic acid (CGA), a type of phenolic acid from Lonicera japonica , also exhibits antioxidation, anti-inflammatory, and bone formation properties. , Recently, more and more researches indicate that both BER and CGA act as potential small-molecule agonists of the Wnt signaling pathway. , Herein, we develop accurate ratiometric nanoagonists (NAs) derived from herbal medicine with the desired potential of accelerating bone formation via inducing Wnt signaling for conquering osteoporosis (Scheme ). BER and CGA, a pair of active ingredients from natural alkaloid and phenolic acid, are chosen to self-assemble into herbal-derived NAs through noncovalent electrostatic, π–π, and hydrophobic interactions with 100% drug loading capacity and stable nanostructure.…”