Dual chemotherapy and photodynamic therapy in an HT-29 human colon cancer xenograft model using SN-38-loaded chlorin-core star block copolymer micelles

Chlorin-core star-shaped block copolymer (CSBC) may self-assemble to form micelles, which act as nanosized photosensitizing agents for photodynamic therapy (PDT) and further encapsulate hydrophobic drugs. This functionalized micellar delivery system is a potential dual carrier for the synergistic combination of photodynamic therapy and chemotherapy for the treatment of cancer. In this study, SN-38 encapsulated CSBC micelles were successfully prepared using a lyophilization-hydration method. Our results show that the prolonged plasma residence time of SN-38/CSBC micelles as compared with free CPT-11 permit increased tumor accumulation and consequently, improved antitumor activity. The combined effects of SN-38/CSBC micelles with PDT were evaluated in an HT-29 human colon cancer xenograft model. Interesting, SN-38/CSBC-mediated PDT synergistically inhibited tumor growth, resulting in up to 60% complete regression of well-established tumors after 3 treatments. These treatments also decreased the microvessel density (MVD) and cell proliferation within the subcutaneous tumors. Therefore, this SN-38/CBSC delivery system has the potential to offer dual therapies for the synergistic combination of PDT and chemotherapy for the treatment of cancer. (C) 2009 Elsevier Ltd. All rights reserved

Development of gelatin nanoparticles with biotinylated EGF conjugation for lung cancer targeting

Since lung cancer is the most malignant cancer today, a specific drug-delivery system has been developed for superior outcome. In this study, gelatin nanoparticles (GPs) employed as native carriers were grafted with NeutrAvidin(FITC) on the particle's surface (GP-Av). Next, the biotinylated epithelial growth factor (EGF) molecules were conjugated with NeutrAvidin(FITC), forming a core-shell-like structure (GP-Av-bEGF) to achieve the enhancement of targeting efficiency. These nanoparticles were applied as an EGF receptor (EGFR)-seeking agent to detect lung adenocarcinoma. The results showed that the modification process had no significant influence on particle size (220 nm) and zeta potential (-9.3 mV). By the in vitro cell culture test, GP-Av-bEGF resulted in higher entrance efficiency on adenocarcinoma cells (A549) than that on normal lung cells (HFL1) because A549 possessed greater amounts of EGFR. We also found that uptake of GP-Av-bEGF by A549 cells was time and dose dependent. Confocal microscopy confirmed the cellular internalization of GP-Av-bEGF, and more fluorescent spots of GP-Av-bEGF nanoparticles were obviously observed as well as lysosomal entrapment in A549. Finally, the delivery was demonstrated by in vivo aerosol administration to cancerous lung of the SCID mice model, and specific accumulation in cancerous lung was confirmed by image quantification. The targeting ability of GP-Av-bEGF was proved in vitro and in vivo, which holds promise for further anti-cancer drug applications. (C) 2007 Elsevier Ltd. All rights reserved