Adjuvant Photothermal Therapy Inhibits Local Recurrences after Breast-Conserving Surgery with Little Skin Damage.

Adjuvant treatments following breast-conserving surgery (BCS) are essential to reduce the risk of local recurrences in patients with breast cancer. However, current adjuvant treatments are based on ionizing radiation, which brings radiation-induced damage and amplifies the risk of death. Here we explore the feasibility of using non-ionizing light to induce photothermal therapy as an adjuvant treatment to BCS. In an orthotopic breast cancer mice model, we demonstrate that adjuvant photothermal therapy (aPTT) decreases the incidence of local recurrences after BCS with no expense of cosmetic outcome. In comparison with conventional photothermal therapy, the technique used in aPTT provides more uniformly distributed light energy and less risk of skin burns and local recurrences. Overall, this work represents a departure from the traditional concept of using PTT as an alternative to surgery and reveals the potential of using PTT as an alternative to adjuvant radiation therapy, which is valuable especially for patients susceptible to radiation damage.

Selectively Sensitizing Malignant Cells to Photothermal Therapy Using a CD44-Targeting Heat Shock Protein 72 Depletion Nanosystem.

Selectively enhance the therapeutic efficacy to malignancy is one of the most important issues for photothermal therapy (PTT). However, most solid tumors, such as triple negative breast cancer (TNBC), do not have identifiable surface markers to distinguish themselves from normal cells, thus it is challenging to selectively identify and eliminate those malignances by PTT. In this report, we hypothesized that, by targeting CD44 (one TNBC-overexpressed surface molecule) and depleting heat shock protein 72 (HSP72, one malignancy-specific-overexpressed thermotolerance-related chaperone) subsequently, the TNBC could be selectively sensitized to PTT and improve the accuracy of treatment. To this end, a rationally designed nanosystem gold nanostar (GNS)/siRNA against HSP72 (siHSP72)/hyaluronic acid (HA) was successfully constructed using a layer-by-layer method. Hydrodynamic diameter and zeta potential analysis demonstrated the formation of GNS/siHSP72/HA having a particle size of 73.2 ± 3.8 nm and a negative surface charge of -18.3 ± 1.6 mV. The CD44-targeting ability of GNS/siHSP72/HA was confirmed by the flow cytometer, confocal microscopic imaging, and competitive binding analysis. The HSP72 silencing efficacy of GNS/siHSP72/HA was ∼95% in complete culture medium. By targeting CD44 and depleting HSP72 sequentially, GNS/siHSP72/HA could selectively sensitize TNBC cells to hyperthermia and enhance the therapeutic efficacy to TNBC with minimal side effect both in vitro and in vivo. Other advantages of GNS/siHSP72/HA included easy synthesis, robust siRNA loading capacity, endosome/lysosome escaping ability, high photothermal conversion efficacy and superior hemo- and biocompatibility.

Recombinant human endostatin endostar suppresses angiogenesis and lymphangiogenesis of malignant pleural effusion in mice.

BACKGROUND: Malignant pleural effusion (MPE) is a common complication of lung cancer. One widely used treatment for MPE is Endostar, a recombined humanized endostatin based treatment. However, the mechanism of this treatment is still unclear. The aim of this study was to investigate the effects of Endostar in mice with MPE. METHODS AND MATERIALS: Lewis lung carcinoma (LLC) cell line expressing enhanced green fluorescent protein (EGFP) was injected into pleural cavity to establish MPE mice model. Mice were randomly divided into four groups. High dose of Endostar (30 mg/kg), low dose of Endostar (8 mg/kg), normal saline, or Bevacizumab (5 mg/kg) was respectively injected into pleural cavity three times with 3-day interval in each group. Transverse computed tomography (CT) was performed to observe pleural fluid formation 14 days after LLC cells injection. Mice were anesthetized and sacrificed 3 days after final administration. The volume of pleural effusion n was measured using 1 ml syringe. Micro blood vessel density (MVD), Lymphatic micro vessel density (LMVD), the expression level of vascular endothelial growth factor A (VEGF-A) and VEGF-C were observed by immunohistochemistry (IHC) staining. RESULTS: The volume of pleural effusion as well as the number of pleural tumor foci, MVD and the expression of VEGF-A were significantly reduced in high dose of Endostar treat group. More importantly, LMVD and the expression of VEGF-C were markedly lower in treat group than those in the other three control groups. CONCLUSION: Our work demonstrated that Endostar played an efficient anti-cancer role in MPE through its suppressive effect on angiogenesis and lymphangiogenesis, which provided a certain theoretical basis for the effectiveness of Endostar on the MPE treatment.