Lotus Seedpod-Inspired Crosslinking-Assembled Hydrogels Based on Gold Nanoclusters for Synergistic Osteosarcoma Multimode Imaging and Therapy

Abstract

Osteosarcoma is difficult to be resected through surgical operations without damage to the bone matrix, while chemotherapy and radiotherapy induce inevitable systemic injury. It is still a major challenge to develop a novel treatment suitable for the complex anatomical structure of the bone. Herein, inspired by lotus seedpods, injectable hydrogels with long-term retention for synergistic osteosarcoma treatment were developed. Gold nanoclusters (GNCs) with strong fluorescence (FL) and computed tomography (CT) imaging effects represented the lotus seeds. The oxidized hyaluronic acid (HA-ALD) chain resembled the stem. HA-ALD and GNCs form crosslinking-assembled hydrogels abbreviated as HG-CAHs through dynamic amide bonds. Compared with DNA-, pH-, and light-mediated assembly, this in situ method induces enhanced photothermal therapy (PTT) ability, ensures high biocompatibility, and retains the imaging function of GNCs, which contribute to lighting up osteosarcoma persistently for further diagnosis and treatment. In addition, the HG-CAHs with outstanding mechanical properties are similar to the lotus seedpods with supportive force and a typical porous structure. They are favorable for the local pH- and near-infrared (NIR)-responsive release of doxorubicin (Dox) owing to the acidic osteosarcoma microenvironment and the Brownian movement. The HG-CAHs ablate osteosarcoma efficiently and reduce metabolic toxicity significantly, which will aid in the development of a new generation of osteosarcoma treatments.

Nanoarchitecture-Integrated Hydrogel Systems toward Therapeutic Applications

“…Upon response to pH and NIR light, HG-CAHs realized to reduce metabolic toxicity and efficiently inhibit osteosarcoma. 122 Apart from these, as an attractive example using a conjugated polymer as PTA, Fan and co-workers fabricated benzoxaborole (BOB)-modified HA (BOB-HA) and fructose-based glycopolymer (PolyFru) as the depot for photosensitizer perylene diimide zwitterionic polymer (PDS), reductant ascorbic acid (Vc), anticancer drug DOX, and photothermal nanoparticles (DB-NPs). 99 Upon NIR irradiation, PDS and Vc converted oxygen to hydrogen peroxide which cleaved the dynamic covalent bonds based on benzoxaborole−carbohydrate interactions, leading to NIR-light-activatable release of DOX and DB-NPs.…”

“…Inspired by this feature of lotus seedpods, Ma et al designed injectable hydrogels with long-term retention to combine with gold nanoclusters (GNCs) and load DOX (HG-CAHs) for fluorescence (FL) and computed tomography (CT) imaging guided synergistic chemo-PTT of osteosarcoma. Upon response to pH and NIR light, HG-CAHs realized to reduce metabolic toxicity and efficiently inhibit osteosarcoma …”

Light-Driven and Metal–Organic Framework Synergetic Loaded DNA Tetrahedral Amplifier for Exonuclease III-Powered All-in-One Biosensing and Chemotherapy in Live Biosystems

“…Therefore, a robust carrier to achieve the synergetic loading of the drug is required . Unlike other frequently used biological carrier materials, including inorganic particles, − polymers, , and two-dimensional membranes, − metal–organic frameworks (MOFs) have hollow spaces (pores) for the packaging of the drug and can be easily surface-modified for linkage to the biosensing system. − Even so, there is a risk of the leakage of the drug from the naked porous structure [ i.e. , the surface aperture of UiO-66 (a frequently used MOF) is approximately 2 nm in diameter].…”

Advances in the Application of Photothermal Composite Scaffolds for Osteosarcoma Ablation and Bone Regeneration

“…This photothermal stimulation has been shown to increase the expression of heat shock proteins and promote the repair of bone defects, indicating favorable osteogenic activity. , Mild PTT can also induce M2 polarization to accelerate the secretion of M2-characteristic cytokines and promote the recruitment of bone mesenchymal stem cells (BMSCs), bone differentiation, and extracellular matrix (ECM) mineralization . There is also a growing number of studies that have shown that BTE scaffolds loaded with PTAs can achieve a win–win situation for tumor ablation and bone repair. − Different types of nano-PTAs are combined with BTE scaffold materials and subsequently implanted into the bone defect site. The tumor ablation effect of the PTAs and the tissue regeneration ability of the scaffold can be fully utilized under laser irradiation of a specific wavelength.…”