phytochlorin and Triple-Negative-Breast-Neoplasms

Photodynamic therapy (PDT) has become a promising treatment option for highly aggressive triple-negative breast cancer (TNBC); however, hypoxia limits the efficacy of PDT and promotes tumour aggression. In this work, we first constructed a multifunctional yolk-shell structured nanoplatform consisting of periodic mesoporous organosilica (PMO) coupled with chlorin e6 (Ce6) and catalase (Catalase) (Yolk-Shell PMO-Ce6@Catalase) for enhanced PDT against TNBC. This nanoplatform has an organic-inorganic hybrid skeleton structure, a uniform size and good stability and biocompatibility. In vitro experiments showed that the nanoplatform has a good ability to generate singlet oxygen. Catalase can convert H

Topics: Catalase; Cell Line, Tumor; Chlorophyllides; Humans; Hydrogen Peroxide; Photochemotherapy; Photosensitizing Agents; Porphyrins; Triple Negative Breast Neoplasms

To develop a treatment modality for triple-negative breast cancer, we investigated the efficacy of a bifunctional theranostic nanoprobes (BN) during Photodynamic Therapy (PDT) on human breast carcinoma and normal human cells. The BN is a 21 nm gold nanoparticles functionalized with Chlorin e6 (Ce6) and Epidermal Growth Factor (EGF). Attachment to gold nanoparticle stabilizes Ce6 while EGF acts as a cancer cell targeting agent. Fluorescence Spectroscopy and Confocal Fluorescence Microscopy revealed a gradual uptake of nanoprobes into cancer cells at an average rate of 63 BN/min. Cell viability assays showed that 0.2 μg/mL BN concentration was highly cytotoxic to cancer cells (86 %), but not normal cells. At this concentration, 58 % cancer cells were necrotic and 38 % apoptotic, while the reactive oxygen species (ROS) was 9-fold higher in cancer cells compared to normal. Overall, results suggest that BN mediated PDT can achieve targeted cancer cell death with high efficiency.

Topics: Animals; Cell Line, Tumor; Chlorophyllides; Epidermal Growth Factor; Gold; Humans; Metal Nanoparticles; Mice; Mice, Inbred BALB C; Mice, Nude; Nanomedicine; Nanoparticles; Photochemotherapy; Photosensitizing Agents; Porphyrins; Triple Negative Breast Neoplasms

Sonodynamic Therapy (SDT) has good targeting and non-invasive advantages in solid cancers, but its antitumor effect is not sufficient to replace traditional treatments. Some studies that combined SDT with chemotherapy or nanoparticles have managed to enhance its efficiency and overcome the side effects of chemotherapy.. In this study, we synthesized and characterized mesoporous silica nanoparticles (MSN-DOX-Ce6) loaded with doxorubicin (DOX) and sonosensitizer, chlorin e6 (Ce6). Then, we conducted in vitro and in vivo experiments to explore the antitumor effect of MSN-DOX-Ce6 under ultrasound (US) treatment.. The characterization tests showed that the nanoparticles are uniformly sized spheres with mesoporous structure, resulting in a high drug-loading efficiency. In the in vitro experiments, MSN-DOX-Ce6 could effectively inhibit cell proliferation under US but not more than other treatment groups. However, the in vivo studies showed that MSN-DOX-Ce6+US has better antitumor effect than DOX+Ce6+US or DOX alone on xenograft tumor-bearing mice.. In summary, MSNs showed a great potential for DOX and Ce6 delivery. We concluded that under US, MSN-DOX-Ce6 nanocomposites increase the antitumor effect of DOX and SDT and thereby are a potential treatment for solid tumors.

Topics: Animals; Antineoplastic Agents; Body Weight; Cell Line, Tumor; Chlorophyllides; Doxorubicin; Drug Liberation; Fluorescence; Humans; Mice; Nanoparticles; Porosity; Porphyrins; Silicon Dioxide; Triple Negative Breast Neoplasms; Tumor Burden; Ultrasonography

Triple-negative breast cancer (TNBC) tumors are heterogeneous, with mesenchymal-like cells at their core and fast proliferating cells on the periphery. It is desirable and beneficial to treat TNBC cells of different phenotypes with the most appropriate drugs. Here, we report a 78 nm, chlorin e6-, docetaxel-, and anti-Twist siRNA-containing polymeric nanoparticle (CDTN) with spatiotemporally specific activity when irradiated by light. Under conditions mimicking superficial tumor tissue with sufficient light input, TNBC cells are mainly killed by the photodynamic therapy (PDT) function of CDTNs. In contrast, under conditions mimicking deep tumor tissue with weak light input, PDT potentiates chemotherapy (CT) and gene therapy (GT) by facilitating the endolysosomal escape of CDTNs. Compared with free drugs, CDTNs improve the intratumoral exposure of docetaxel and anti-Twist siRNA by 2.5- and 2-fold, respectively. When combined with laser irradiation applied at the time of maximal intratumoral accumulation, the CDTNs significantly inhibit the growth of primary tumors and their lung metastasis (both >80%) by killing the peripheral cells, mainly through PDT and prohibiting the growth and metastasis of deep cells through PDT as enhanced CT and GT. On the contrary, dual-modality nanomedicine lacking CT, GT, or PDT showed fast primary tumor growth, poor metastasis control, or both, respectively. This study reveals the spatiotemporally specific mechanism of CDTNs in treating metastatic TNBC and highlights the importance of combined therapy in treating TNBC.

Topics: Animals; Antineoplastic Agents; Chlorophyllides; Docetaxel; Female; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Photochemotherapy; Photosensitizing Agents; Porphyrins; RNA, Small Interfering; RNAi Therapeutics; Triple Negative Breast Neoplasms; Twist-Related Protein 1