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Intratumorally Injected Photothermal Agent-Loaded Photodynamic Nanocarriers for Ablation of Orthotopic Melanoma and Breast Cancer

DOI:10.1021/acsbiomaterials.8b01111 期刊:ACS Biomaterials Science & Engineering 出版年份:2019 更新时间:2025-09-23 15:23:52
摘要: Traditional chemotherapy of cancers may lead to serious adverse reactions due to little drug distribution in tumors. Here, a combination of photothermal therapy (PTT) and photodynamic therapy (PDT) was used for local treatment of orthotopic melanoma and breast cancer via intratumoral (i.t.) injection of photothermal agent-loaded photodynamic nanocarriers. A hydrophobic derivative of indocyanine green, DCC, was synthesized and entrapped into a pH-sensitive photosensitizer-core copolymer, PDCZP, to form DCC@PDCZP. The nanocarriers showed remarkable fluorescence, high singlet oxygen quantum yields, and strong photothermal effect. Flow cytometry suggested that the nanocarriers were efficiently internalized by cancer cells. Near infrared thermal imaging and fluorescence self-imaging showed that the i.t. injected DCC@PDCZP mainly remained in the tumors but the intravenous (i.v.) nanocarriers were distributed a little. One i.t. injection of DCC@PDCZP was enough to ablate the orthotopic B16-F10 and 4T1 mouse tumors under 830 nm and 660 nm irradiation at 4 hours post-injection. More importantly, no local recurrences were found though scabs were formed at 9 days post-treatment. The major anticancer mechanisms included improvement of cancer cell necrosis due to hyperthermia, inhibition of neovascularization, and enhancement of cell apoptosis. The i.t. injection of PTT/PDT nanoformulations is thus a promising local treatment of superficial tumors.
作者: Xiaodong Sun,Bo Zhuang,Mengmeng Zhang,Heliu Jiang,Yiguang Jin
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To develop and evaluate a combined photothermal and photodynamic therapy approach using intratumorally injected nanocarriers for effective ablation of orthotopic melanoma and breast cancer with minimal side effects and prevention of recurrence.

The intratumoral injection of DCC@PDCZP nanocarriers combined with 830 nm and 660 nm light irradiation effectively ablated orthotopic melanoma and breast cancer tumors without local recurrence. The synergistic PTT/PDT approach enhanced cancer cell necrosis, inhibited neovascularization, and promoted apoptosis, making it a promising local treatment for superficial tumors.

The combinational PTT/PDT may be suitable only for non-metastatic tumors as its effect is limited to local sites; some mice died due to metastasis in breast cancer studies; potential issues with light penetration depth for deeper tumors.

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