Targeting drug cocktail hydrogel platform for inhibiting tumor growth and metastasis

Abstract

The combination therapy could overcome the limitation of monotherapy to inhibit tumor recurrence and metastasis, but is usually constrained by complex fabrication processes. Here, a tunable hydrogel platform was developed using different silk nanocarriers, which independently achieve flexible functional optimization of various drugs. Silk nanorods (SNR) were modified with cRGDfK peptides to achieve targeting ability to tumor vessels and then loaded with hydrophobic vascular inhibitor Combretastatin A4 (CA4). The loading of CA4 and the targeted modification could be tuned to enhance the destruction of tumor vessels. Both hydrophilic doxorubicin (DOX) and hydrophobic paclitaxel (PTX) were co-loaded on silk nanofibers (SNF) to form injectable hydrogels with optimized combination chemotherapy. The drug-laden SNR and SNF were blended directly to form injectable hydrogels without the compromise of drug biological activity. Both the targeting modification of SNR and the optimized co-delivery of DOX and PTX improved the therapeutic efficiency in vitro and in vivo. The long-term inhibition of tumor recurrence and metastasis was achieved through the injectable silk nanocarriers, which are superior to previous combination chemotherapy systems of DOX and PTX. The gradual modular fabrication process and simple physical blending endowed the systems with high flexibility and tunability, suggesting a suitable platform for designing a drug cocktail system.

Keywords

• Silk nanocarriers
• Drug cocktail
• Injectable hydrogel
• Combination therapy
• Tumor recurrence