Ultrasound assisted gene and photodynamic synergistic therapy with multifunctional FOXA1-siRNA loaded porphyrin microbubbles for enhancing therapeutic efficacy for breast cancer.

Ultrasound assisted gene and photodynamic synergistic therapy with multifunctional FOXA1-siRNA loaded porphyrin microbubbles for enhancing therapeutic efficacy for breast cancer. Biomaterials. 2018 May 03;173:58-70 Authors: Zhao R, Liang X, Zhao B, Chen M, Liu R, Sun S, Yue X, Wang S Abstract To improve the non-invasive therapeutic efficacy for ER positive breast cancer (ER+ BC), we fabricated a multifunctional FOXA1 loaded porphyrin microbubble to combine photodynamic therapy (PDT) and gene therapy of FOXA1 knockdown (KD) with ultrasound targeted microbubble destruction (UTMD) technology under the guidance of contrast enhanced ultrasound (CEUS). Cationic porphyrin microbubbles (CpMBs) were firstly fabricated from a porphyrin grafted lipid with two cationic amino groups (PGL-NH2) and fluorocarbon inert gas of C3F8. Porphyrin group in the CpMBs monolayer could be used as a photosensitizer for PDT, while amino groups could adsorb siRNA through electrostatic interaction for FOXA1 KD, which could inhibit the proliferation of estrogen-dependent ER+ BC. This system showed high photosensitizer and gene loading content. Moreover, CpMBs/siRNA can be converted into nanoparticles with low-frequency pulsed ultrasound (LFUS) exposure, which increase the transfection efficiency of siRNA (∼4 fold) and the porphyrin uptake (∼8 fold) in MCF-7 (a human breast cancer cell line, ER+) by sonoporation effect. In vivo, UTMD was performed under the g...
Source: Biomaterials - Category: Materials Science Authors: Tags: Biomaterials Source Type: research