Cancer stem cells (CSCs) are proposed to account for the initiation of cancer metastasis, but their accessibility remains a great challenge. This study reports deep tumor-penetrated biomimetic nanocages to augment the accessibility to CSCs fractions in tumor for anti-metastasis therapy. The nanocages can load photothermal agent of 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide (DBN) and chemotherapeutic epirubicin (EBN) to eradicate CSCs for photothermal-chemotherapy of breast cancer metastasis. In metastatic 4T1-indcued tumor model, both DBN and EBN can efficiently accumulate in tumor sites and feasibly permeate throughout the tumor mass. These biomimetic nanosystems can be preferentially internalized by cancer cells and effectively accessed to CSCs fractions in tumor. The DBN+laser/EBN treatment produces considerable depression of primary tumor growth, drastically eradicates around 80% of CSCs fractions in primary tumor, and results in 95.2% inhibition of lung metastasis. Thus, the biomimetic nanocages can be a promising delivery nanovehicle with preferential CSCs-accessibility for effective anti-metastasis therapy.
Keywords: cancer metastasis; cancer stem cells; deep tumor penetration; drug delivery; nanocages.