Bioinspired Tumor‐Targeting and Biomarker‐Activatable Cell‐Material Interfacing System Enhances Osteosarcoma Treatment via Biomineralization

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.

Recent research progress on tumour-specific responsive hydrogels

“…The PBA molecules in this conjugate selectively recognize SA molecules overexpressed on the cancer cell surface, while the DDDEEK peptide induces biomineralization, ultimately leading to cancer cell death. 32 To selectively target osteosarcoma cells, an enzyme-activatable pY domain was strategically inserted between DDDEEK and PBA to confer a response to the overexpression of ALP in osteosarcoma cells. ALP cleaves the phosphate groups of pY, initiating the self-assembly of hydrophobic and electrostatically induced supramolecular complexes.…”

Photo-Driven In Situ Solidification of Whole Cells through Inhibition of Trogocytosis for Immunotherapy

“…Biomineralization is the process by which inorganic matter ions undergo nucleation, crystallization, and growth in the presence of proteins to form inorganic matter [ 24 , 25 ]. Recently, patients with biomineralized calcium carbonate nanoparticles found within the tumor tissues had a significantly higher survival rate compared to patients without these nanoparticles [ 26 , 27 ]. Tang’s group exploits the fact that folic acid residues can induce calcium ion calcification on the surface of tumor cells, which can effectively inhibit tumor growth and metastasis without damaging normal cells [ 28 – 30 ].…”

MiR-150-5p inhibits cell proliferation and metastasis by targeting FTO in osteosarcoma

“…While the amalgamation of surgical intervention and neoadjuvant chemotherapy has enhanced the five-year survival prognosis for newly diagnosed patients, considerable disparity in chemotherapeutic drug sensitivity continues to pose a substantial hindrance [3]. This impediment is markedly accentuated in patients manifesting metastasis or disease recurrence [4]. Consequently, the exploration of innovative targets from a mechanistic viewpoint becomes vital to comprehend the fundamental etiologies of metastasis and drug resistance.…”