Biodegradable Nanocomposite with Dual Cell‐Tissue Penetration for Deep Tumor Chemo‐Phototherapy
Xueting Pan, Pengju Li, Lintao Bai, Junjie Ma, Shanshan Li, Fengrong Zhang, Shuang Liu, Qingyuan Wu, Heyun Shen, Huiyu Liu
Abstract
Chemo-phototherapy, as a promising cancer combination therapy strategy, has attracted widespread attention. However, the complex tumor microenvironment restricts the penetration depth of chemo-phototherapy agents in the tumor region. Here, biodegradable amphiphilic gelatin (AG) wrapped nanocomposite (PRDCuS@AG) composed of doxorubicin and copper sulfide (CuS)-loaded dendrimer is designed for deep tumor chemo-phototherapy. PR in PRDCuS@AG represents arginine-conjugated polyamidoamine dendrimer. PRDCuS@AG can rapidly biodegrade into PRDCuS by matrix metalloproteinases under near-infrared light irradiation. The resulted PRDCuS harbors dual cell-tissue penetration ability, which can effectively penetrate deep into the tumor tissue. In particular, PRDCuS@AG achieves photoacoustic imaging-guided synergistic chemo-phototherapy with 97% of tumor inhibition rate. Moreover, PRDCuS@AG can further degrade into 3 nm ultrasmall CuS, which can be eliminated from the body after treatment to avoid side effects. This strategy provides an insight that the development of chemo-phototherapy agents with high penetration ability to overcome the limitation of current deep tumor therapy.