Alendronate Triggered Dual‐Cascade Targeting Prodrug Nanoparticles for Enhanced Tumor Penetration and STING Activation of Osteosarcoma

Abstract

The complex physiological environment in bone tissue poses a challenge to the efficient delivery of chemotherapeutic agents for osteosarcoma (OS) treatment; hence, an efficient drug delivery system designed for OS is highly desired. Herein, alendronate (Ale)‐based cationic platinum prodrug nanoparticles (Ale NP) are developed, which exhibit cascade responsiveness to the OS tumor microenvironment. With Ale triggered bone targeting and charge reversal effects, Ale NP demonstrates superior capacity for achieving deep penetration into dense OS tissues. Furthermore, Ale NP can induce dendritic cell (DC) maturation via activation of the cyclic GMP‐AMP synthase‐stimulator of interferon genes (cGAS‐STING) pathway using platinum drugs. The highly potent phenanthridine (Pt(II)) can be released in the presence of overexpressed glutathione (GSH) in tumor cells, thereby achieving dual‐targeted cascade delivery of cationic platinum drugs in OS. Notably, Ale NP not only effectively eliminates the tumor in the internal region of OS but also acts as a potent STING agonist to effectively reverse the suppressive microenvironment of OS. Overall, Ale‐triggered dual‐cascade targeting prodrug nanoparticles significantly improve drug targeting and penetration in OS, hence paving a promising avenue for the clinical treatment of OS.

Stimulus‐Responsive Copper Complex Nanoparticles Induce Cuproptosis for Augmented Cancer Immunotherapy

“…The penetration capacity of Cu(I) NP was further evaluated in this model. [ 21 ] Fluorescence signals originating from the nanoparticles can be observed at different section depths. CLSM images show that strong red fluorescence can be detected at the center of tumor spheroids, indicating the penetration ability of Cy5.5‐Cu(I) NP in 3D tumor spheroids (Figure 2C ).…”

Nanomedomics

“…Chemotherapy is an essential therapy for tumors that can inhibit various types of solid and nonsolid tumors. However, some chemotherapy drugs, such as platinum-based drugs, have defects such as low bioavailability and severe side effects. − To address these deficiencies, many nanomaterials have been utilized as carriers to load platinum drugs. − Despite this, there is still a lack of research on the mechanism of action of these nanomedicines, which adversely affects their further clinical translation. To solve this problem, Wang et al used RNA-seq and metabolomics to study the mechanism of nanobased platinum drugs.…”

A Bioactive Injectable Hydrogel Regulates Tumor Metastasis and Wound Healing for Melanoma via NIR‐Light Triggered Hyperthermia

“…The cyclic GMP–AMP synthase (cGAS) – stimulator of interferon genes (STING) signaling pathway, as an important cytoplasmic DNA‐sensing pathway, takes part in regulating cancer immune response by triggering the production of type I interferons (IFN). [ 8 ] Notably, manganese ion (Mn 2+ ) has been shown to activate STING pathway. [ 9 ] When activated by Mn 2+ , STING can facilitate the production of type I interferons and other pro‐inflammatory cytokines, boosting the immune system to detect and fight against cancer.…”