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One Minute, Sub-One-Watt Photothermal Tumor Ablation Using Porphysomes, Intrinsic Multifunctional Nanovesicles
Published on: September 17, 2013
Disrupting stromal barriers to enhance photothermal-chemo therapy using a halofuginone-loaded Janus mesoporous
Rui Tang1, Meng Dang1, Xiaojun Zhang2
1Key Laboratory for Organic Electronics and Information Displays and Institute of Advanced Materials, Jiangsu Key Laboratory for Biosensors, Jiangsu National Synergetic Innovation Centre for Advanced Materials, Nanjing University of Posts and Telecommunications, Nanjing, 210046 Jiangsu, PR China.
Abstract:
Dense tumor stroma is the physiological barrier in drug delivery that prevents anticancer drugs from entering the tumor, thereby seriously limiting the drugs' therapeutic effect. In this study, a Janus nanoplatform consisting of periodic mesoporous organosilica-coated platinum nanoplatforms (JPMO-Pt) and anti-stroma drug halofuginone (HF) (denoted as JPMO-Pt-HF), was developed to deplete the tumor stroma and synergistically treat breast cancer in BALB/c mice. The prepared JPMO-Pt had a uniform size of 245 nm, a good dispersion, an excellent in vitro and in vivo biocompatibility, and a high loading capacity for HF (up to 50 μg/mg). The antitumor experiments showed that the survival rate of 4 T1 cells exhibited an obvious downward trend when the cells were incubated with the JPMO-Pt-HF and irradiated with 808 nm laser. Moreover, the cell survival rate was only about 10% at 48 h when the HF concentration was 2.0 μg/mL. Notably, JPMO-Pt-HF under irradiation had an excellent synergistic therapeutic effect on tumor cells. In vivo antitumor experiment further showed that the JPMO-Pt-HF, in combination with laser irradiation, could minimize tumor growth, showing significantly better effects than those observed for the case of monotherapy involving photothermal therapy (PTT) (152 vs. 670 mm3, p < 0.0001) and HF (152 vs. 419 mm3, p = 0.0208). In addition, immunohistochemistry of tumor tissues indicated that JPMO-Pt-HF obviously reduced the relative collagen and α-smooth muscle actin (α-SMA) area fraction. Taken together, this research designs a new platform that not only possesses the ability to degrade the tumor matrix but also combines PTT and chemotherapeutic effects, and holds promise for effective tumor treatment.
Insights
This study developed a Janus nanoplatform (JPMO-Pt-HF) to break down dense tumor stroma, enhancing chemotherapy and photothermal therapy (PTT) for effective breast cancer treatment.
Area of Science:
- Biomedical Engineering
- Materials Science
- Oncology
Background:
- Dense tumor stroma impedes drug delivery and limits therapeutic efficacy.
- Developing strategies to overcome the stromal barrier is crucial for effective cancer treatment.
Purpose of the Study:
- To develop a Janus nanoplatform (JPMO-Pt-HF) for depleting tumor stroma.
- To investigate the synergistic therapeutic effects of the nanoplatform combined with photothermal therapy (PTT) and chemotherapy for breast cancer.
Main Methods:
- Fabrication of periodic mesoporous organosilica-coated platinum nanoplatforms (JPMO-Pt) loaded with halofuginone (HF).
- In vitro studies on 4T1 breast cancer cells involving laser irradiation.
- In vivo antitumor experiments in BALB/c mice with JPMO-Pt-HF and laser irradiation.
- Immunohistochemical analysis of tumor tissues to assess stroma reduction.
Main Results:
- JPMO-Pt-HF demonstrated high drug loading capacity and biocompatibility.
- Combined JPMO-Pt-HF treatment with laser irradiation significantly inhibited 4T1 cell survival.
- In vivo studies showed minimized tumor growth with JPMO-Pt-HF and laser irradiation, outperforming monotherapies.
- Immunohistochemistry confirmed reduced collagen and α-SMA, indicating stroma degradation.
Conclusions:
- The developed Janus nanoplatform effectively degrades tumor stroma.
- JPMO-Pt-HF combined with PTT and chemotherapy offers a promising synergistic approach for breast cancer treatment.

