Targeting the extracellular matrix of ovarian cancer using functionalized, drug loaded lyophilisomes

Area of Science:

• Oncology
• Biotechnology
• Drug Delivery

Background:

• Epithelial ovarian cancer has a high mortality rate, necessitating novel therapeutic strategies.
• The tumor extracellular matrix (stroma) presents opportunities for targeted drug delivery.
• Highly sulfated chondroitin sulfate E (CS-E) is abundant in ovarian cancer stroma and is a potential therapeutic target.

Purpose of the Study:

• To functionalize drug-loaded lyophilisomes for specific targeting of the ovarian cancer stroma via CS-E.
• To evaluate the efficacy of CS-E-targeted lyophilisomes in inducing cancer cell death.

Main Methods:

• Lyophilisomes (albumin-based biocapsules) were functionalized with single-chain antibodies against CS-E.
• Antibody conjugation was achieved using sortase-mediated ligation and bioorthogonal click chemistry.
• In vitro studies assessed targeting specificity and drug-induced cytotoxicity in a CS-E-rich environment.

Main Results:

• Antibody-functionalized lyophilisomes specifically targeted CS-E in the ovarian cancer stroma.
• Lyophilisomes induced cancer cell death through extracellular doxorubicin release in a CS-E-rich microenvironment.
• CS-E-rich stroma was also identified in breast, lung, and colon cancers, suggesting broader applicability.

Conclusions:

• CS-E-targeted lyophilisomes represent a promising strategy for ovarian cancer therapy.
• This approach demonstrates the potential of using chondroitin sulfate variants as a "hook" for targeted drug delivery in various solid tumors.
• Matrix-based therapy targeting tumor stroma holds potential for improved patient outcomes across multiple cancer types.