Lactosome-Conjugated siRNA Nanoparticles for Photo-Enhanced Gene Silencing in Cancer Cells

The A3B-type Lactosome comprised of poly(sarcosine)3-block-poly(l-lactic acid), a biocompatible and biodegradable polymeric nanomicelle, was reported to accumulate in tumors vivo via the enhanced permeability retention (EPR) effect. Recently, cellular uptake particles through incorporation cell-penetrating peptide (CPP), L7EB1. However, ability as drug delivery carrier has not been established. Herein, we have developed method conjugate with ATP-binding cassette transporter G2 (ABCG2) siRNA for inducing vitro apoptosis cancer cell lines PANC-1 NCI-H226. L7EB1 facilitates efficiency but does deliver into cytosol. To establish photoinduced cytosolic dispersion siRNA, photosensitizer loaded L7EB1-Lactosome prepared, 5,10,15,20-tetra-kis(pentafluorophenyl)porphyrin (TPFPP) showed superiority dispersion. We exploited combined effects by endosomal escape TPFPP efficiently ABCG2 cytosol gene silencing. Moreover, silencing ABCG2, protoporphyrin IX (PpIX) transporter, also mediated death 5-aminolevulinic acid (ALA)-mediated PpIX accumulated photodynamic therapy (PDT). synergistic capability L7EB1/TPFPP/siRNA-Lactosome complex enabled both PDT.