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Bioinspired Tumor-Targeting and Biomarker-Activatable Cell-Material Interfacing System Enhances Osteosarcoma
Xiao Yang1,2,3,4, Simin Gao5, Boguang Yang1
1Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, Hong Kong, 999077, China.
Abstract:
Osteosarcoma is an aggressive malignant tumor that primarily develops in children and adolescents. The conventional treatments for osteosarcoma often exert negative effects on normal cells, and chemotherapeutic drugs, such as platinum, can lead to multidrug resistance in tumor cells. Herein, this work reports a new bioinspired tumor-targeting and enzyme-activatable cell-material interface system based on DDDEEK-pY-phenylboronic acid (SAP-pY-PBA) conjugates. Using this tandem-activation system, this work selectively regulates the alkaline phosphatase (ALP) triggered anchoring and aggregation of SAP-pY-PBA conjugates on the cancer cell surface and the subsequent formation of the supramolecular hydrogel. This hydrogel layer can efficiently kill osteosarcoma cells by enriching calcium ions from tumor cells and forming a dense hydroxyapatite layer. Owing to the novel antitumor mechanism, this strategy neither hurts normal cells nor causes multidrug resistance in tumor cells, thereby showing an enhanced tumor treatment effect than the classical antitumor drug, doxorubicin (DOX). The outcome of this research demonstrates a new antitumor strategy based on a bioinspired enzyme-responsive biointerface combining supramolecular hydrogels with biomineralization.
Insights
This study introduces a novel bioinspired hydrogel system that targets osteosarcoma cells. The system activates with enzymes, forming a layer that kills cancer cells without harming normal cells or causing drug resistance.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Oncology
Background:
- Osteosarcoma is an aggressive bone cancer primarily affecting children and adolescents.
- Conventional treatments for osteosarcoma have limitations, including negative effects on normal cells and the development of multidrug resistance.
- There is a need for novel therapeutic strategies that specifically target cancer cells and overcome treatment resistance.
Purpose of the Study:
- To develop a bioinspired, enzyme-activatable cell-material interface system for targeted osteosarcoma treatment.
- To investigate the efficacy of a supramolecular hydrogel formed by SAP-pY-PBA conjugates in killing osteosarcoma cells.
- To evaluate the system's ability to avoid harming normal cells and prevent multidrug resistance.
Main Methods:
- A novel bioinspired system using DDDEEK-pY-phenylboronic acid (SAP-pY-PBA) conjugates was synthesized.
- The system was designed to be activated by alkaline phosphatase (ALP) on cancer cell surfaces, triggering hydrogel formation.
- The mechanism involved calcium ion enrichment and hydroxyapatite layer formation for osteosarcoma cell death.
Main Results:
- The SAP-pY-PBA conjugates selectively anchored and aggregated on osteosarcoma cells, forming a supramolecular hydrogel.
- The formed hydrogel effectively killed osteosarcoma cells through biomineralization, creating a hydroxyapatite layer.
- The novel strategy demonstrated superior antitumor effects compared to doxorubicin (DOX) and showed no toxicity to normal cells.
Conclusions:
- The developed enzyme-responsive biointerface system offers a new strategy for osteosarcoma treatment by combining supramolecular hydrogels and biomineralization.
- This approach provides a targeted and effective method for killing osteosarcoma cells while circumventing common treatment challenges like drug resistance and normal cell toxicity.
- The study highlights the potential of bioinspired, enzyme-activatable materials in advancing cancer therapy.
